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Atherogenic Index Reduction and Weight Loss in Metabolic Syndrome Patients Treated with A Novel Pectin-Enriched Formulation of Bergamot Polyphenols

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Bergamot flavonoids counteract dyslipidemia and hyperglycemia but fail to induce a significant weight loss. Here, we evaluated the efficacy of bergamot polyphenol extract complex (BPE-C), a novel bergamot juice-derived formulation enriched with flavonoids and pectins, on several metabolic syndrome parameters. Obese patients with atherogenic index of plasma (AIP) over 0.34 and mild hyperglycemia were recruited to a double-blind randomized trial comparing two doses of BPE-C (650 and 1300 mg daily) with placebo. Fifty-two subjects met the inclusion criteria and were assigned to three experimental groups. Fifteen subjects per group completed 90 days-trial. BPE-C reduced significantly fasting glucose by 18.1%, triglycerides by 32% and cholesterol parameters by up to 41.4%, leading to a powerful reduction of AIP (below 0.2) in the high dose group. The homeostasis model assessment of insulin resistance (HOMA-IR) and insulin levels were also reduced. Moreover, BPE-C decreased body weight by 14.8% and body mass index by 15.9% in BPE-C high group. This correlated with a significant reduction of circulating hormones balancing caloric intake, including leptin, ghrelin and upregulation of adiponectin. All effects showed a dose-dependent tendency. This study suggests that food supplements, containing full spectrum of bergamot juice components, such as BPE-C efficiently induce a combination of weight loss and insulin sensitivity effects together with a robust reduction of atherosclerosis risk.
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Nutrients 2019, 11, 1271; doi:10.3390/nu11061271 www.mdpi.com/journal/nutrients
Article
Atherogenic Index Reduction and Weight Loss in
Metabolic Syndrome Patients Treated with A Novel
Pectin-Enriched Formulation
of Bergamot Polyphenols
Antonio Soccorso Capomolla
1
, Elzbieta Janda
2,3,
*, Sara Paone
3
, Maddalena Parafati
2,3
,
Tomasz Sawicki
2,4
, Rocco Mollace
2,3
, Salvatore Ragusa
2
and Vincenzo Mollace
2,3,5,
*
1
Villa dei Gerani Hospital, 89900 Vibo Valencia, Italy; scapomolla@gmail.com
2
Department of Health Sciences, Magna Graecia University, Campus Germaneto, 88100 Catanzaro, Italy;
mparafati@unicz.it (M.P.); t.sawicki@pan.olsztyn.pl (T.S.); rocco.mollace@gmail.com (R.M.);
sragusa@unicz.it (S.R.)
3
Interregional Research Center for Food Safety and Health, 88100 Catanzaro, Italy; sara.paone06@gmail.com
4
Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences,
10-748 Olsztyn, Poland
5
San Raffaele, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Pisana, 00163 Rome, Italy
* Correspondence: janda@unicz.it (E.J.); mollace@unicz.it (V.M.);
Tel.: 0039-366-6215493 (E.J.); 0039-366-6215492 (V.M.)
Received: 5 May 2019; Accepted: 3 June 2019; Published: 4 June 2019
Abstract: Bergamot flavonoids counteract dyslipidemia and hyperglycemia but fail to induce a
significant weight loss. Here, we evaluated the efficacy of bergamot polyphenol extract complex
(BPE-C), a novel bergamot juice-derived formulation enriched with flavonoids and pectins, on
several metabolic syndrome parameters. Obese patients with atherogenic index of plasma (AIP)
over 0.34 and mild hyperglycemia were recruited to a double-blind randomized trial comparing
two doses of BPE-C (650 and 1300 mg daily) with placebo. Fifty-two subjects met the inclusion
criteria and were assigned to three experimental groups. Fifteen subjects per group completed 90
days-trial. BPE-C reduced significantly fasting glucose by 18.1%, triglycerides by 32% and
cholesterol parameters by up to 41.4%, leading to a powerful reduction of AIP (below 0.2) in the
high dose group. The homeostasis model assessment of insulin resistance (HOMA-IR) and insulin
levels were also reduced. Moreover, BPE-C decreased body weight by 14.8% and body mass index
by 15.9% in BPE-C high group. This correlated with a significant reduction of circulating hormones
balancing caloric intake, including leptin, ghrelin and upregulation of adiponectin. All effects
showed a dose-dependent tendency. This study suggests that food supplements, containing full
spectrum of bergamot juice components, such as BPE-C efficiently induce a combination of weight
loss and insulin sensitivity effects together with a robust reduction of atherosclerosis risk.
Keywords: atherosclerosis; metabolic syndrome; insulin resistance; bergamot polyphenol fraction
(BPF); body mass index; clinical trial; cardiovascular risk factors; obesity
1. Introduction
Metabolic syndrome (MetS) is a cluster of several cardiometabolic risk factors, including
hyperglycemia or glucose intolerance, high levels of triglycerides (TG) and low-density lipoprotein
cholesterol (LDL-C) and low levels of high-density lipoprotein cholesterol (HDL-C), hypertension,
abdominal adiposity and obesity [1,2]. It is diagnosed based on the presence of at least three metabolic
Nutrients 2019, 11, 1271 2 of 13
alterations listed above, but insulin resistance and visceral adiposity are the most common features
of MetS pathophysiology [3]. MetS prevalence ranges from 10% up to 85% of general population
worldwide and is higher in industrialized countries. In Europe, the mean MetS incidence is 24.3%
and it increases with advancing age (from 3.7 in the group aged 20–29 years to more than 30% in the
subjects 70 years and older) [3]. Around 20%–25% of Italians have MetS and reflect the European
mean [4]. The treatment of MetS is the main strategy to prevent cardiovascular complications, such
as atherogenesis [1]. Atherosclerotic lesions can form in the presence of an unfavorable plasma lipid
profile that can be characterized by atherogenic index of plasma (AIP). It is defined as logarithm [log]
of the ratio of TG to HDL-C plasma concentrations and thus it depends mainly on circulating fat
levels. AIP values over 0.21 indicate high risk of atherosclerosis and inversely correlate with
cardiovascular health [5,6]. AIP can be also considered as a strong and independent predictor for
coronary artery disease [5,7,8].
The energy homeostasis and, in particular body fat and food intake, are altered in MetS and this
is associated with abnormalities in circulating hormones with a pivotal role in the regulation of
energy balance in the body, such as adiponectin, leptin, and ghrelin. In fact, both the levels of these
hormones, as well their ratio are known to be altered in MetS patients [9]. Adiponectin is considered
cardioprotective since it improves lipid and glucose metabolism, increases insulin sensitivity [9].
Several observational studies have reported an inverse association between adiponectin serum levels
and body weight (BW), total cholesterol (TotChol), TG levels, blood pressure, and insulin resistance,
and a positive association with HDL-C levels [10]. On the contrary, there is a positive correlation of
MetS parameters, such as insulin resistance and adiposity with plasma concentrations of leptin [11].
In fact, elevated plasma leptin is considered as an independent cardiovascular risk factor [12]. Ghrelin
is a meal-initiating, acylated peptide secreted primarily by the stomach an endogenous ligand for the
growth hormone receptor, which rapidly stimulates food intake when exogenously administered
[13]. Plasma ghrelin concentrations correlate with appetite and food intake [14].
Overwhelming evidence suggests that many of the features of metabolic syndrome, including
hormonal imbalance can be efficiently treated with natural approaches, such as fiber and polyphenol-
rich diet and polyphenol-rich food supplements [15,16]. One of the most promising and effective food
supplements used for the management of metabolic syndrome is Bergamot Polyphenol Fraction
(BPF). BPF is a yellow powder extracted from bergamot (Citrus bergamia Risso et Poiteu) fruits,
containing high levels of flavonoids, including 38 ± 2% of flavanones such as naringin, neoericitrin,
neohesperidin, bruteridin and melitidin [17,18]. BPF was shown to counteract several features of
MetS. In particular, TG and TotChol levels were strongly reduced, both alone as well as in
combination with statins [19–21]. In line with this property, BPF has a particularly strong effect on
lipid metabolism in the liver [17,22]. Accordingly, it prevents non-alcoholic fatty liver disease
(NAFLD) induced by cafeteria diet (CAF) in rats [22], and in the same animal model boosts the
therapeutic effect of the normocaloric diet on CAF-induced non-alcoholic steato-hepatitis (NASH)
[17]. There is also an evidence indicating that BPF attenuates NAFLD and NASH in patients [23,24].
Hepatoprotective effects of BPF are associated with its ability to induce autophagy [18,22,25]. The
proautophagic activity of BPF suggests that it may stimulate energy expenditure and prevent weight
gain. Yet, little evidence has been collected on weight-loss effects of BPF.
In addition, the experimental data suggest that non-flavonoid components of fruits, including
pectins, as well as other yet unidentified compounds, may enhance the pharmacological responses
to flavonoid phytocomplex [26,27]. This may depend on microbiota-mediated or microbiota-
independent mechanisms [28,29].
For this reason, we decided to evaluate the effect of the exsiccated bergamot juice extract
containing 8% pectins, 8% vitamin C, enriched with BPF to increase the flavonoid content in a small-
scale clinical trial on MetS patients with moderate hyperglycemia. The first aim of the study was to
evaluate changes in serum lipid and glucose contents after 90 days treatment with two doses of BPE-
C. The secondary aim was to evaluate a possible BW loss elicited by BPE-C treatment as well as its
impact on serum levels of adiponectin, leptin and ghrelin in the same group of patients within the 90
days study period.
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2. Materials and Methods
2.1. Food Supplement Used in The Study
BPE-C also known with a proprietary name as BΠE-complexTM was developed and kindly
provided by Herbal and Antioxidant Derivatives (H&AD) S.r.l. (Bianco, RC, Italy). BPE-C contains
around 80% of BPE, which is a bergamot juice extract characterized by a reduced amount of
carbohydrates and citric acid and around 20% of BPFTM containing mainly bergamot juice flavonoids.
The latter is added to increase the amount of five main bergamot flavanones (neoeriocitrin, naringin,
neohesperidin, melitidin, bruteridin) to 38 ± 2%. BPE was obtained from a fresh bergamot juice by a
partial pulp and citric acid removal and essential oil evaporation followed by an enzymatic reduction
of carbohydrate content and a subsequent spray drying according to a proprietary procedure
developed by H&AD. BPE contains >8% pectins and >8% ascorbic acid (vitamin C) and appears as a
yellow powder. BPFTM was obtained from a clarified bergamot juice according to a patented
procedure (No. EP 2 364 158 B1) described also in Mollace et al. [20] Polyphenol content was routinely
determined by high-pressure liquid chromatography [18,20].
2.2. Subjects
Participants, males and females between 40 to 80 years old, were recruited from MetS patients
of San Raffaele IRCCS, Pisana, Rome, Italy and Villa dei Gerani Hospital, Vibo Valencia, Italy, who
were not originally receiving lipid-lowering therapy. Inclusion criteria were: obesity with BMI >26,
high TG >200 mg/dL, high TotChol >200 mg/dL, moderate glycemia: 130 >Glu > 100 mg/dL.
Exclusion criteria were gastritis, presence of other diagnosed malignancies, pregnancy or breast-
feeding, lack of compliance defined as not using the correct BPE-C dose or placebo for >1 week), and
inability to give informed consent. The study protocol was given approval by the Institutional Ethics
Committee and written informed consent was obtained from participants. This trial was registered
at the Magna Graecia University of Catanzaro (UNICZ) Clinical Trials Registry
(http://www.unicz.it/.../) under Trial No. 182/2016.
2.3. Study Design
This study was designed as a randomized, double-blind, placebo-controlled trial. Patients who
met the inclusion criteria were assigned to either BPE-C low, n = 17 (one capsule = 650 mg BPE-C) or
BPE high, n = 18, (2 capsules = 1300 mg BPE-C) treatment groups, or a matched placebo group (n =
17) for a period of 90 days. Placebo capsules contained the same amount of maltodextrin. BPE-C dose
(650 mg once or twice daily) was established based on preliminary observations and the use of the
same dose in our previous trial in MetS individuals [20]. All the recruited patients were advised to
follow a healthy diet, rich in fruits and vegetables and poor in fats and carbohydrates (1200 Cal/day)
during the study and a qualitative compliance was assessed by an interview. The patients were seen
every seven days during the study. Serum aspartate aminotransferase, alanine aminotransferase,
creatine kinase, blood urea nitrogen and creatinine and blood cell counts were measured before and
after therapy to monitor for possible side effects.
2.4. Blood Sampling and Measurements
Blood samples were collected after overnight fasting at the beginning and at the end of study.
The serum was collected from the samples left to clot for about 30 min and then centrifuged at 750 g
for 10 min. Sera were aliquoted and frozen at 80°C until measurement.
TotChol, LDL-C, HDL-C, TG and glucose levels in serum samples of patients were determined
by commercial colorimetric and enzymatic assay kits (BioSystems S.A., Barcelona, Spain). Serum
concentrations of insulin, leptin, adiponectin and ghrelin was determined by commercially available
ELISA kits (Millipore, Merck S.p.a., Milano, Italy). The sensitivity of detection of leptin were 0.78–100
ng/ml, 1.5–100 μg/ml for adiponectin and 50–5000 pg/ml for ghrelin.
Nutrients 2019, 11, 1271 4 of 13
Weight and height were measured according to standard procedures. BMI were calculated as
weight in kilograms divided by height in meters squared. The approximate insulin resistance (IR)
was calculated by HOMA-IR using the following formula: glucose(mmol/L) × insulin (μU/mL))/22.5
[17]. AIP was calculated as log value of the ratio between TG and HDL-C concentrations expressed
in mmol/L.
2.5. Statistical Analyses
Statistical analyses were performed using GraphPad Prism version 8.0.0 for Windows,
(GraphPad Software, San Diego, CA, USA). Data were expressed as a mean ± standard deviation (SD)
or as a median ± SD, as indicated. Bartlett's test was performed on each set of data to ensure that
variance of the sets was homogenous. In case of homogenous set of data, one-way ANOVA with
Bonferroni’s multiple comparison test was performed as appropriate. In case of heterogenous data,
Kruskal–Wallis followed by Dunn’s tests were carried out. For groups comparison of categorical
values, such as patient sex, Pearson’s chi-square test was performed with Statistica software (Stat
Soft, Tulsa, OK, USA).
3. Results
Fifty-two subjects met the inclusion criteria and were assigned to three experimental groups
BPE-C high (n = 18), BPE-C low (n = 17) or placebo (n = 17). Forty-five subjects completed the trial.
The total of seven subjects in the three groups did not complete the study due to lack of compliance.
The number of drop-outs was not different between the study groups. BPE-C was also well tolerated
during the study. However, similarly to our previous report [20] regarding pharmacological effects
of BPFTM, there were few reports of moderate gastric pyrosis in BPE-C low (n = 2) and BPE-C high (n
= 1) groups. Headache (n = 2) and constipation (n = 1) were reported adverse events in the placebo
group. However, none of the patients taking BPE-C interrupted the treatment due to the above
adverse effects.
BPE-C and placebo groups were comparable at baseline with respect to age, sex, smoking habits
(Table 1), and with respect to all study parameters: BW (Figure 1A), BMI (Figure 1C) and serum levels
of TotChol (Figure 2A), LDL-C (Figure 2C), HDL-C (Figure 2E), TG (Figure 3A), and glucose (Figure
3C). It was also true when treatment groups where compared for baseline parameters, except for BMI
that was significantly higher in BPE-C high when compared to BPE-C low group (Figure 1C). This
baseline difference should not influence significantly BMI reduction parameter, which is calculated
as a difference between BMI before and BMI after the treatment.
Table 1. The baseline characteristics of patients.
Variables Placebo
(n = 15)
BPE-C
low
(n = 15)
BPE-C
high
(n = 15)
p value
(Placebo vs BPE-C
low)
p value
(Placebo vs BPE-C
high)
p value
(BPE-C low vs
high)
Age (years) 55.6 ±
7.4 59 ± 7.6 56.1 ± 10.9 0.889 0.999 0.999
Weight (kg) 83.4 ±
9.5 82.5 ± 10 84.6 ± 9.7 0.443 0.661 0.999
Sex (M/F) 8/7 7/8 9/6 0.715 0.713 0.464
Smokers
(Y/N) 0/15 0/15 0/15 - - -
Age and BW data sets were analyzed by one-way ANOVA and Bonferroni’s post-hoc test. p values
for sex distribution in three experimental groups were calculated using Pearson’s chi square test. High
p values confirm that the three patient groups were homogenously randomized.
Nutrients 2019, 11, 1271 5 of 13
Figure 1. BPE-C reduces body mass (BW) in MetS patients. BW values for baseline A) and B) after 90-
days intervention on MetS patients assigned to three experimental groups (Placebo, BPE-C low and
high). C) percent reduction calculated for B. BMI values for baseline D) and E) after 90 days as in B.
F) percent reduction calculated for E. The scatter plots represent 15 patients for each group. Horizontal
lines and vertical bars represent the mean ± SD, respectively. Statistical analysis was performed by
ANOVA followed by Bonferroni’s pos-hoc test. The analysis revealed significant differences
compared to Placebo at # p 0.05 or #### p 0.0001 and between BPE-C treatment groups at * p 0.05,
*** p 0.001 or **** p 0.0001.
After 90 days of treatment all analyzed body and serum parameters were significantly changed
in BPE-C high groups, in contrast to the placebo group and in several cases also in BPE-C low groups.
Notably, BW decreased significantly only in BPE-C high group (Figure 1B), but when expressed as
BMI the change was significant for both low and high BPE-C groups (Figure 1E). Moreover, when
compared to the baseline, BW decreased significantly by 10% and 14.8% (Figure 1C) and BMI by 10%
and 15.9% (Figure 1F) in BPE-C low and high treatment groups, respectively.
The effect of BPE-C supplementation was particularly striking and significant in case of all
routinely measured cholesterol parameters, which appeared strongly decreased as in case of TotChol
and LDL-C (Figure 2B and E) or elevated when compared to Placebo as in case of HDL-C (Figure
2H). The response to BPE-C was also strongly dose-dependent with p 0.01 for all three cholesterol
parameters (Figure 2B, E and H). Moreover, when compared to baseline TotChol changed
significantly by -23.7% and -28.4% (Figure 2C) and LDL-C by -30.4% and -41.4% (Figure 2F). This was
associated with a marked increase in HDL-C by 10.9% and 26.4% in BPE-C low and high treatment
groups, respectively (Figure 2I).
Patients’ TG also responded strongly and dose-dependently to BPE-C low and high doses when
compared to Placebo (Figure 3B) with mean reductions calculated from the baseline values such as
27.1% and 31.9%, respectively (Figure 3C). Finally, fasting serum glucose was significantly decreased
after BPE-C intervention, when compared to Placebo in both treatment groups (Figure 3B). In
particular, the mean changes, compared to the baseline glucose, were -12.1% and -18% in low and
high treatment groups, respectively (Figure 3F). In addition, the data supported a direct and
significant dose-response relationship with respect to low and high doses of BPE-C in case of TG and
glucose endpoint values (Figure 3B and E).
Finally, when “percent changes from baseline” data sets were subjected to statistical analysis we
observed significant differences for BW and BMI (Figure 1C and F), LDL-C, HDL-C (Figure 2F and I)
Nutrients 2019, 11, 1271 6 of 13
and glucose (Figure 3D) between BPE-C high and low treatment groups. In all other comparisons of
the treatment groups a clear tendency to dose-dependence was observed, statistically significant
according to Bonferroni’s, but not to Dunn’s multiple comparisons tests.
Figure 2. BPE-C reduces cholesterol levels in MetS patients. A) Blood total cholesterol (TotChol)
before (baseline) A) and B) after 90-days intervention on MetS patients assigned to three experimental
groups (Placebo, BPE-C low and high). C) percent reduction calculated for B. D) LDL-C levels for
baseline and E) after treatment as in B. F) percent reduction calculated for E. G) HDL-C levels for
baseline and H) after treatment as in B. I) percent change calculated for H. The scatter plots represent
15 participants for each group. Statistical differences were analyzed by ANOVA (A, B, D, E, G and H)
or by Kruskal–Wallis (C, F and I) followed by Bonferroni’s or Dunn’s post-hoc tests, respectively. The
analysis revealed significant differences compared to Placebo at # p 0.05; ## p 0.01 or #### p 0.0001
and between BPE-C treatment groups at * p 0.05; ** p 0.01 or **** p 0.0001. Horizontal lines
represent the mean ± SD.
Nutrients 2019, 11, 1271 7 of 13
Figure 3. BPE-C reduces triglycerides and fasting serum glucose levels in MetS patients. A) TG levels
before (baseline) A) and B) after 90-days intervention on MetS patients assigned to three experimental groups
(Placebo, BPE-C low and high). C) percent reduction calculated for B. D) Baseline fasting serum glucose levels
and E) after 90 days as in B. F) percent reduction calculated for E. Statistical differences were analyzed by
ANOVA (A, B, D and E) or Kruskal–Wallis (C and F) tests followed by Bonferroni’s or Dunn’s post-hoc tests,
respectively. The analysis revealed significant differences in BPE-C treatment groups when compared to
Placebo at ## p 0.01; ### p 0.001 or #### p 0.0001 and between BPE-C treatment groups at * p 0.05; ** p
0.01 or **** p 0.0001. Horizontal lines represent the mean ± SD.
Next, AIP was calculated to evaluate the risk of atherogenesis and its complications after the
treatment with BPE-C. The analysis revealed a significant AIP reduction (p 0.001), noticeable in both
low and high dose groups. In particular, the starting AIP mean values 0.45 and 0.46 ± 0.04 (Figure
4A) were reduced to 0.19 ± 0.03 and 0.27 ± 0.05 in patients treated with high and low BPE-C dose,
respectively (Figure 4B). In addition, the difference between low and high BPE-C groups was
statistically significant (Figure 4B and C).
Figure 4. BPE-C reduces atherogenic index of plasma (AIP) in MetS patients. A) AIP before treatment
and B) after 90-days treatment with BPE-C or placebo. C) Percent reduction of AIP after treatment.
Statistical differences were analyzed by ANOVA test followed by Bonferroni’s post-hoc test (A and
B) or Kruskal–Wallis test followed by Dunn’s test(C). Horizontal bars show the mean of 15 patients ±
SD. The analysis revealed a significant AIP decrease after the treatment with BPE-C when compared
to Placebo at ## p 0.01 or ### p 0.001 for both doses of BPE-C. The response to BPE-C was dose-
dependent at *** p 0.001 (B) or at * p 0.05, when % reductions were compared (C).
Nutrients 2019, 11, 1271 8 of 13
Next, we checked if the substantial reduction of hyperglycemia correlated with the improvement
in insulin sensitivity in the treatment groups, approximated as reduced insulin resistance (HOMA-
IR index). Between-group comparison revealed a highly significant and dose-dependent decrease of
HOMA-IR in the BPE-C low and high groups compared to Placebo group (Figure 5B), which
corresponded to significant mean changes by -7.2% and -18.1%, with respect to the baseline values in
low and high dose groups, respectively (Figure 5C).
Figure 5. BPE-C improves insulin sensitivity by a significant reduction of HOMA-IR index in MetS
patients. A) HOMA-IR before treatment and B) after 90-days treatment with BPE-C or placebo. C)
Percent change of HOMA-IR with respect to baseline values. Statistical differences were analyzed by
ANOVA test followed by Bonferroni’s post-hoc test (A and B) and Kruskal–Wallis test followed by
Dunn’s test (C). Horizontal bars show the mean of 15 patients ± SD. The analysis revealed a highly
significant HOMA-IR decrease after the treatment with BPE-C at ## p 0.01 or ### p 0.001 for low
and high doses, respectively. The response to BPE-C was dose-dependent at * p 0.05.
As expected, a significant reduction was also observed in serum insulin concentrations (p < 0.001)
in BPE-C high patients (Table 2). Nevertheless, the response, was not significant in BPE-C low when
compared to Placebo group (Table 2).
Next, we analyzed the levels of energy balance hormones regulating fat mass and food intake.
There was also no significant difference between BPE-C groups and placebo group in terms of
baseline serum adiponectin and leptin, as well as for insulin and ghrelin levels (p > 0.05, Table 2).
Posttreatment analysis revealed a significant decrease of serum leptin concentrations in both BPE-C
groups (p < 0.05) compared to the baseline and to the placebo groups (Table 2). Likewise, the serum
ghrelin was significantly reduced in the BPE-C high and low versus placebo group (p < 0.001) (Table
2). Finally, there was an increase in serum adiponectin concentrations in both BPE-C low and high
treatment groups, which was statistically significant even in BPE-C low group compared to placebo
group (p = 0.003) (Table 2).
Nutrients 2019, 11, 1271 9 of 13
Table 2. Plasma levels of energy balance hormones and insulin, before (baseline) and after 90 days
intervention on MetS patients assigned to three experimental groups (Placebo, BPE-C low and high).
Experimental groups
Biomarker
Insulin
(IU/L)
Leptin
(ng/ml)
Ghrelin
(pg/ml)
Adiponectin
(mg/mL)
Baseline Placebo 20 ± 1.6 22.1 ± 1.1 619 ± 24 19.5 ± 1.3
Baseline BPE-C low 20 ± 1.5 22.6 ± 1.4 623 ± 19 19.3 ± 1.5
Baseline BPE-C high 19.6 ± 2.4 22 ± 2.3 624 ± 38 19.3 ± 1.4
Placebo 19.5 ± 2.6 22.3 ± 1.3 620 ± 22 18.6 ± 2.4
BPE-C low 16.6 ± 1.4 19.3 ± 2.0 581 ± 22 22.9 ± 2.5
BPE-C high 14.2 ± 1.2 17.3 ± 0.4 530 ± 21 23.5 ± 1.4
p values
Placebo vs BPE-C low 0.067 KW 0.013 KW < 0.001 0.003
Placebo vs BPE-C high < 0.001 KW < 0.001 KW < 0.001 < 0.001
BPE-C high vs BPE-C low 0.007 KW 0.046 KW < 0.001 0.078
Change after treatment (%)
Placebo -2,5 ± 6.7 -0.5 ± 4 0.3 ± 2 -4.6 ± 11.6
BPE-C low -16.5 ± 6.5 -13.9 ± 11 -6.6 ± 2.4 18.1 ± 12.8
BPE-C high -26.4 ± 10.7 -20.5 ± 8.9 -14.9 ± 2.9 22.3 ± 9.6
p values
Placebo vs BPE-C low 0.001 0.002
KW < 0.001 < 0.001
Placebo vs BPE-C high < 0.001 < 0.001 KW < 0.001 < 0.001
BPE-C high vs BPE-C low 0.006 0.490 KW 0.007 0.942
Statistical analysis was performed by ANOVA and Bonferroni’s post-hoc test (where not specified)
or by Kruskal–Wallis followed by Dunn’s post-hoc, where indicated by KW. The mean ± SD out of
15 patients is shown for each parameter. Statistically significant p values (p < 0.05) are in bold.
4. Discussion
The findings of this randomized, placebo-controlled trial suggest a significant amelioration of
dyslipidemia and insulin sensitivity after 90 days of BPE-C supplementation to a group of MetS
patients characterized by an elevated AIP (over 0.34) and moderate hyperglycemia (up to 130 mg/L).
Compared to previous clinical studies performed with BPF on a larger group MetS patients, the
supplementation of BPE-C yielded similar results with respect to the reduction of TotChol, LDL-C
and TG and increase of HDL-C [20]. In particular. they were slightly better for cholesterol parameters
and weaker for TG. For example, a potent mean decrease by 41.4 ± 2.3% in LDL-C levels were
recorded in BPE-C high group, which was a stronger response than in the previous study, in BPF
high dose group (mean 36%). This might be due to a longer treatment time (90 vs 30 days), 30%
larger dose of BPE-C used in the present study as well as a specific and more homogenous profile of
patients recruited for the present study. For the same reason, it is difficult to evaluate the impact of
the new formulation of BPE-C with respect to the standard BPF used in the previous study [20].
Nevertheless, these data confirm that BPE-C is an efficient remedy against dyslipidemia in MetS
patients with moderately elevated glycemia.
The severity of dyslipidemia, such as high TG levels and low HDL-C, correlating with small size
of LDL particles, determine high AIP and thus atherogenic risk. The value of AIP as a predictive
biomarker for atherosclerosis and coronary artery disease has been confirmed in several recent
studies on men and post-menopausal women [6–8,30,31]. The presented here data indicate a strong
reduction of AIP to mean values 0.19 ± 0.03 and 0.27 ± 0.05 in patients treated with high and low BPE-
C dose, respectively. Since AIP below 0.21 is considered to correlate with a low cardiovascular risk
[6] we can conclude that the high dose of BPE-C is sufficient to switch the patients from high to low
risk of atherosclerosis and related cardiovascular complications.
Another important finding of this study is the dose-dependent reduction of BW and BMI by 10%
to 16% in patients receiving low and high dose of BPE-C for 90 days, respectively. This is the first
clinical trial demonstrating a significant BW loss with bergamot derived nutraceuticals on MetS
patients. The previous clinical studies testing pharmacological effects of BPF either did not examine
BW/BMI changes [19–21,23,24] or reported not significant BMI reduction after 120 days of BPF (1300
mg daily) supplementation [32] or found a positive preventive effect of BPF supplementation on
Nutrients 2019, 11, 1271 10 of 13
second-generation antipsychotic drugs-induced weight gain in psychiatric patients [33]. However,
the latter findings were not confirmed in a larger study [34]. In pre-clinical studies in rats, BPF effect
on body mass was reported in the prevention-type studies [22,35], but not in the parallel intervention-
type study on obese rats with CAF diet-induced NASH [17]. In addition, the prevention-type studies,
demonstrated only a modest 8% reduction in BW gain upon 14 weeks treatment with BPF, probably
due to a very aggressive type of obesogenic diet used to induce MetS with NASH, which is the CAF
diet in rats [22,35].
Lack of a significant changes in BMI in clinical and intervention-type preclinical studies with
flavonoid-only supplementation is not surprising. In fact, only one study out of 28 reviewed studies
addressing the effects of dietary polyphenols on BW reported a modest weight loss after very long
application of Mediterranean diet (two years) to MetS patients [16,36]. In another review, 10 out 34
papers reported on a modest weight loss induced by polyphenol extracts, in most of the cases derived
from green tea [37].
Thus, dietary polyphenols rarely improve BMI parameters when applied to patients as purified
polyphenol extracts. In contrast, many clinical and preclinical studies with pectins and other dietary
fibers report on moderate, but significant BW loss in parallel with other health benefits related to
pectin consumption [26]. Pectins usually limit BW gain by reducing food intake in rodents [28,38,39].
In humans, pectins lessen the appetite and their consumption is inversely associated with BW gain
[40]. These observations indicate that body-weight loss effects of the reported here clinical study can
be attributed to pectin enrichment. However, we cannot exclude that other components of bergamot
juice present in BPE-C may also contribute to BW loss.
The protective effects against diet–induced obesity are largely attributed to pectin fermentation
by gut bacteria and the uptake of metabolites, such as short chain fatty acids (SCFAs) [41,42]. For
example, SCFA metabolism in the liver regulates glucose and lipid metabolism and energy
homeostasis [43]. A recent study demonstrates that several different types of dietary fibers reduce
BW in laboratory animals and largely different gut bacteria profiles can contribute to beneficial effects
of dietary fibers [28], while other studies suggest that probiotic effect of pectins depends not only on
their chemical and physical characteristics [44], but also on their source.
Energy homeostasis and, in particular body fat and food intake, as well as BMI are regulated by
a complex interplay of blood hormones such a as adiponectin, leptin and ghrelin. Accordingly, the
effects on BMI observed in this study were mirrored by a significant reduction in leptin levels in both
treatment groups and significant upregulation of adiponectin levels. These changes likely reflect a
possible reduction in body fat in patients at the end of the study.
Concurrent with a decrease in circulating leptin, plasma ghrelin concentrations increase
following weight loss from an energy-restricted diet [14]. However, ghrelin levels may also decrease
reflecting reduced appetite and food intake [13]. In fact, the patients in this trial experienced less
appetite and they had significantly lower levels of circulating ghrelin after 90 days of BPE-C
treatment. Similar observations were reported in a recent curcumin study. Daily curcumin and
piperine supplementation for 12 weeks, increased adiponectin and reduced leptin and ghrelin levels,
although the mean reduction in ghrelin was not significant in this study [45].
5. Conclusions
In conclusion, the present human study reports on a powerful reduction of AIP to a low risk
value in a selected sub-group of MetS patients after 90 days treatment with BPE-C. It also provides
the first evidence that bergamot juice-derived food supplements enriched with pectins and vitamin
C, such as BPE-C significantly stimulate weight loss, improve insulin sensitivity and reduce
circulating insulin, leptin, and ghrelin levels, while increasing significantly the levels of
cardioprotective adiponectin. This study also confirms previously reported robust improvement of
dyslipidemia, i.e. reduction of TG, TotChol and LDL-C by daily supplementation of bergamot
flavonoids to the daily diet. Future studies should be undertaken to ascertain the impact of pectin
and ascorbic acid, as well as other components of bergamot juice in this novel nutraceutical
formulation on the observed beneficial effects.
Nutrients 2019, 11, 1271 11 of 13
Author Contributions: Conceptualization, E.J., S.R. and V.M.; Data curation, A.S.C., S.P., R.M. and V.M.; Formal
analysis, E.J., M.P. and T.S.; Funding acquisition, V.M.; Investigation, A.S.C., S.P., R.M. and V.M.; Methodology,
A.S.C.; Project administration, S.P. and V.M.; Resources, A.S.C.; Software, T.S.; Supervision, V.M.; Visualization,
M.P. and T.S.; Writing–original draft, E.J.; Writing–review & editing, E.J.
Funding: This research was funded by: Magna Graecia University, Catanzaro; PON3a-00359 Research and
Competitiveness grant and Nutramed Consortium (PON03PE 00078); Herbal and Antioxidant Derivatives
(H&AD) S.r.l., Bianco (RC), Italy. T.S. was supported by KNOW consortium 'Healthy Animal—Safe Food'
MS&HE No. 05-1/KNOW2/2015".
Conflicts of Interest: The authors declare no conflict of interest. The funders had no role in the collection,
analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
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The relationship between low LDL-C (cholesterol associated with low-density lipoprotein) and a lower relative risk of developing cardiovascular disease (CVD) has been widely demonstrated. Although from a pharmacological point of view, statins, ezetimibe and PCSK inhibitors, alone or in combination are the front and center of the therapeutic approaches for reducing LDL-C and its CV consequences, in recent years nutraceuticals and functional foods have increasingly been considered as a valid support in the reduction of LDL-C, especially in patients with mild/moderate hyperlipidemia - therefore not requiring pharmacological treatment - or in patients intolerant to statins or other drugs. An approach also shared by the European Atherosclerosis Society (EAS). Of the various active ingredients with hypolipidemic properties, we include the artichoke (Cynara cardunculus, Cynara scolymus) and the bergamot (Citrus bergamia) which, thanks essentially to the significant presence of polyphenols in their extracts, can exert this action associated with a number of other complementary inflammation and oxidation benefits. In light of these evidence, this review aimed to describe the effects of artichoke and bergamot in modifying the lipid and inflammatory parameters described in in vitro, in vivo and clinical studies. The available data support the use of standardized compositions of artichoke and bergamot extracts, alone or in combination, in the treatment of mild to moderate dyslipidemia, in patients suffering from metabolic syndrome, hepatic steatosis, or intolerant to common hypolipidemic treatments.
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The present study aimed to explore the correlation of atherogenic index of plasma (AIP) with angiographic progression of coronary artery disease (CAD). AIP was defined as the base 10 logarithm of the ratio of the triglyceride to high-density lipoprotein cholesterol concentration. The extent of coronary lesion was assessed by the Gensini Score (GS) system and angiographic progression was defined as the GS rate of change per year >1 point. A total of 896 patients with suspected CAD who underwent coronary computed tomography angiography twice at intervals of >6 months were included. Baseline AIP was positively correlated with remnant cholesterol (r = .644, P < .001). When patients were assigned into four groups according to baseline AIP quartiles, the incidence of CAD progression significantly increased across the quartiles of AIP (Q1 [lowest]: 23.7 vs Q2: 29.9 vs Q3: 33.9 vs Q4 [highest]: 34.8%; P = .042). After multivariate adjustment, the odds ratio for CAD progression was 1.89 when comparing the highest to the lowest quartile of AIP (95% confidence interval: 1.18–3.02; P = .008). Therefore, AIP was independently correlated with angiographic progression of CAD beyond conventional risk factors, suggesting that AIP may play a role in early risk stratification as a simple surrogate of residual risk.
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Obesity is influenced by environmental, behavioral, and genetic factors; particularly genes related to the regulation of lipids and addictive behavior. Food craving (FC) is a physiological and behavioral response that triggers the intense desire to ingest food, particularly food with high energy, fat, and/or sweet content. Objective: To evaluate the relationship between the prevalence of FC in obese subjects and blood lipids as well as to determine the transcriptional modulation of CART, DRD2, and FTO. Method: Transverse, comparative, and randomized study including 21 obese participants (BMI, ≥30 kg/m2] and 20 normal weight participants (BMI, ≤25 kg/m2). We determined CART, DRD2, and FTO expressions; evaluated blood lipid levels; and obtained trait scores on the Food Craving Questionnaire-Trait, a multifactorial instrument validated for the Mexican population. Results: The DRD2 expression was significantly increased (p = 0.027) and the CART expression was significantly decreased (p = 0.001) in obese participants compared with normal weight participants. The FTO expression did not show significant differences. Food Craving Questionnaire-Trait showed scores of ≥72 in obese participants. Conclusions: Linear regression model analysis showed that FC is a predictor of atherogenic index (ATH), independently of BMI, and of the gene expression modulation of CART and DRD2.
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Objective: The value of atherogenic index of plasma (AIP) as a predictive biomarker for coronary artery disease (CAD) remains controversial. In addition, whether AIP is associated with the risk of acute coronary syndrome (ACS) in very young adults has not been well established. Methods: We consecutively collected very young adults (≤35 years of age) undergoing coronary angiography (CAG) at Anzhen Hospital, between January 2008 and December 2017. Total of 1, 478 very young participants, including 1, 059 ACS patients and 419 non-CAD subjects, were enrolled in the present study. Results: Very young patients with ACS had higher AIP level compared with non-CAD participants (0.35 ± 0.30 vs 0.21 ± 0.33, P < 0.001). According to Gensini Score (GS) and number of lesion vessel, patients were divided into four groups, respectively. With the elevated GS score and number of lesion vessels, the AIP level increased gradually (Pfor trend all< 0.05). Multivariate logistic regression analyses suggested that AIP remained to be independently associated with the presence of ACS and was superior to traditional lipid profiles (for AIP, OR = 2.930, 95% CI = 1.855-4.627, P < 0.001; for total cholesterol, OR = 1.152, 95% CI = 1.048-1.266, P = 0.003; for triglyceride, OR = 1.078, 95% CI = 0.991-1.172, P = 0.079; for low-density lipoprotein cholesterol, OR = 1.046, 95% CI = 1.015-1.078, P < 0.001), after adjustment for other traditional confounders. Moreover, the prevalence of ACS, acute myocardial infarction, unstable angina pectoris and the value of GS were also elevated as AIP quartiles increased (Pfor trend < 0.001). Subgroup analysis based on gender revealed that AIP was only independently associated with the ACS risk in male. Conclusions: AIP was independently associated with the presence and severity of ACS in very young patients in a gender-dependent manner, which might be superior to traditional lipid profiles.
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Objective: Hyperlipemia represents an independent risk factor in the development of atherosclerosis in patients undergoing type 2 diabetes mellitus (DM). Moreover, the pharmacological treatment of dyslipemia in patients undergoing type 2 DM (e.g. by means of statins), is accompanied by relevant side effects and oral supplementation with natural antioxidants, such as Citrus polyphenols, has recently been suggested to improve cardioprotection in such patients. However, due to the poor gastrointestinal absorption of polyphenols, novel formulations have recently been developed for getting a better bioavailability of polyphenolic rich fractions of citrus species extract rich in polyphenols. Methods: Here, we investigated the effect of standard bergamot polyphenolic fraction (BPF®) as well as of its phytosomal formulation (BPF Phyto), in patients with type 2 DM and hyperlipemia. A randomized, double blind, placebo-controlled study was carried out in 60 patients suffering from type 2 DM and mixed hyperlipemia. Patients were divided into three groups: one receiving placebo, the second receiving standard BPF and the third BPF Phyto. Results: In the groups receiving BPF and BPF Phyto, a significant reduction of fasting plasma glucose, serum LDL cholesterol and triglycerides accompanied by increased HDL cholesterol was observed. This effect was associated with significant reduction of small dense atherogenic LDL particles, as detected by means of proton NMR Spectroscopy, thus confirming the hypolipemic and hypoglycemic effect of bergamot extract both when using standard formulation as well as BPF Phyto. No differences were seen in the therapeutic response among groups receiving BPF and BPF Phyto, thus suggesting a substantial bioequivalence in their hypoglycemic and hypolipemic profile. However, when comparing the pharmacokinetic profile of naringin (the major component of BPF) and its metabolites, in patients treated with BPF Phyto, an at least 2,5 fold increase in its absorption was found, confirming in human studies the better profile of BPF Phyto compared to standard BPF. Conclusion: These data suggest that better absorption and tissue distribution of BPF Phyto formulation represents an innovative approach in supplementation treatments of cardiometabolic disorders.
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Wrong alimentary behaviors and so-called "junk food" are a driving force for the rising incidence of non-alcoholic fatty liver disease (NAFLD) among children and adults. The "junk food" toxicity can be studied in "cafeteria" (CAF) diet animal model. Young rats exposed to CAF diet become obese and rapidly develop NAFLD. We have previously showed that bergamot (Citrus bergamia Risso et Poiteau) flavonoids, in the form of bergamot polyphenol fraction (BPF), effectively prevent CAF diet-induced NAFLD in rats. Here, we addressed if BPF can accelerate therapeutic effects of weight loss induced by a normocaloric standard chow (SC) diet. 21 rats fed with CAF diet for 16 weeks to induce NAFLD with inflammatory features (NASH) were divided into three groups. Two groups were switched to SC diet supplemented or not with BPF (CAF/SC±BPF), while one group continued with CAF diet (CAF/CAF) for 10 weeks. BPF had no effect on SC diet-induced weight loss, but it accelerated hepatic lipid droplets clearance and reduced blood triglycerides. Accordingly, BPF improved insulin sensitivity, but had little effect on leptin levels. Interestingly, the inflammatory parameters were still elevated in CAF/SC livers compared to CAF/CAF group after 10 weeks of dietary intervention, despite over 90% hepatic fat reduction. In contrast, BPF supplementation decreased hepatic inflammation by reducing interleukin 6 (Il6) mRNA expression and increasing anti-inflammatory Il10, which correlated with fewer Kupffer cells and lower inflammatory foci score in CAF/SC+BPF livers compared to CAF/SC group. These data indicate that BPF mediates a specific anti-inflammatory activity in livers recovering from NASH, while it boosts lipid-lowering and anti-diabetic effects of the dietary intervention.
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Dietary fibers (DF) can prevent obesity in rodents fed a high-fat diet (HFD). Their mode of action is not fully elucidated, but the gut microbiota have been implicated. This study aimed to identify the effects of seven dietary fibers (barley beta-glucan, apple pectin, inulin, inulin acetate ester, inulin propionate ester, inulin butyrate ester or a combination of inulin propionate ester and inulin butyrate ester) effective in preventing diet-induced obesity and links to differences in cecal bacteria and host gene expression. Mice (n = 12) were fed either a low-fat diet (LFD), HFD or a HFD supplemented with the DFs, barley beta-glucan, apple pectin, inulin, inulin acetate ester, inulin propionate ester, inulin butyrate ester or a combination of inulin propionate ester and inulin butyrate ester for 8 weeks. Cecal bacteria were determined by Illumina MiSeq sequencing of 16S rRNA gene amplicons. Host responses, body composition, metabolic markers and gene transcription (cecum and liver) were assessed post intervention. HFD mice showed increased adiposity, while all of the DFs prevented weight gain. DF specific differences in cecal bacteria were observed. Results indicate that diverse DFs prevent weight gain on a HFD, despite giving rise to different cecal bacteria profiles. Conversely, common host responses to dietary fiber observed are predicted to be important in improving barrier function and genome stability in the gut, maintaining energy homeostasis and reducing HFD induced inflammatory responses in the liver.
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Background: Dyslipidemia is one of the most important factors for coronary artery disease (CAD). Atherogenic index of plasma (AIP) is a novel indicator involved in dyslipidemia. However, the relation between AIP and CAD in postmenopausal women remains unclear. We hypotheses that AIP is a strong predictive indicator of CAD in postmenopausal women. Methods: A propensity score matching case-control study including 348 postmenopausal CAD cases and 348 controls was conducted in the present study. Results: Compared with controls, CAD patients had higher levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (APOB), but lower high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-1 (APOA-1). The values of nontraditional lipid profiles, including non-HDL-C, TC/HDL-C, LDL-C/HDL-C, non-HDL-C/HDL-C (atherogenic index, AI), TC∗TG∗LDL/HDL-C (lipoprotein combine index, LCI), log(TG/HDL-C) (atherogenic index of plasma, AIP) and APOB/APOA-1 were all significantly higher in the CAD patients. The results of Pearson correlation analyses showed AIP was positively and significantly correlated with TC (r = 0.092, P < 0.001), TG (r = 0.775, P = 0.015), APOB (r = 0.140, P < 0.001), non-HDL-C (r = 0.295, P < 0.001), TC/HDL-C (r = 0.626, P < 0.001), LDL-C/HDL-C (r = 0.469, P < 0.001), AI (r = 0.626, P < 0.001), LCI (r = 0.665, P < 0.001), APOB/APOA-1(r = 0.290, P < 0.001) and was negatively correlated with APOA-1 (r = - 0.278, P < 0.001) and HDL-C (r = - 0.665, P < 0.001). In the multivariate logistic regression analysis, AIP was an independent predictor of CAD. After adjusting for the traditional clinical prognostic factors including diabetes and hypertension, we found AIP could be an independent risk factor for CAD (odds ratio [OR], 3.290; 95% confidence interval [CI], 1.842-5.877, P < 0.001). After adjusting for multiple clinical factors include diabetes, hypertension, smoking, heart ratio, fasting blood glucose, we found AIP also could a powerful risk factor, OR = 3.619, 95%CI (2.003-6.538), P < 0.001. Conclusion: The present study indicated that AIP might be a strong marker for predicting the risk of CAD in postmenopausal women.
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Metabolic syndrome (MetS) represents a cluster of metabolic and cardiovascular complications, including obesity and visceral adiposity, insulin resistance, dyslipidemia, hyperglycemia and hypertension, which directly increase the risk of cardiovascular diseases (CVD) and diabetes mellitus type 2 (DM2). Patients with arthritic diseases, such as rheumatoid arthritis and osteoarthritis, have a higher incidence of CVD. Although recent advances in the treatment of arthritic diseases, the incidence of CVD remains elevated, and MetS has been identified as a possible link between CVD and arthritic diseases. Chronic low-grade inflammation associated with obesity has been established as a significant contributing factor to the increased prevalence of MetS. Adipokines, which play important physiological roles in metabolic activities contributing to the pathogenesis of MetS, are also involved in the regulation of autoimmune and/or inflammatory processes associated with arthritic diseases. Therefore, MetS and dysregulated secretion of pro-inflammatory adipokines have been recognized as a molecular link between CVD and arthritis diseases. In the present paper, we review recent evidence supporting the role played by adipokines, in particular leptin, adiponectin, and lipocalin-2, in the modulation of the immune system, MetS and arthritic diseases. The underlying cellular and molecular mechanisms are discussed, as well as potential new therapeutic strategies.
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Body fat mass increases when energy intake exceeds energy expenditure. In the long term, a positive energy balance will result in obesity. The worldwide prevalence of obesity has increased dramatically, posing a serious threat to human health. Therefore, insight in the pathogenesis of obesity is important to identify novel prevention and treatment strategies. This review describes the physiology of energy expenditure and energy intake in the context of body weight gain in humans. We focus on the components of energy expenditure and the regulation of energy intake. Finally, we describe rare monogenetic causes leading to an impairment in central regulation of food intake and obesity.
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Background and aims We aimed to evaluate the link between inflammatory score [consisting of C-reactive protein (CRP) and white blood cells], serum uric acid (SUA) and atherogenic index of plasma (AIP) and the cardiovascular health (CVH) score. Methods We used the cross-sectional National Health and Nutrition Examination Survey database. Statistical analyses accounted for the survey design and sample weights. Results Overall, there were 23,004 participants (mean age = 47.2 years, 46.5% males). Participants with an ideal CVH level had the highest ratio of poverty to income (3.62%, p < 0.001), as well as lower levels of CRP, SUA and AIP (p < 0.001 for all comparisons). In adjusted linear regression, a significant negative association was observed between inflammatory score (β = −0.052, p < 0.001), SUA (β = −0.041, p < 0.001) and AIP (β = −0.039, p < 0.001) and CVH score, i.e. participants with a better (greater) CVH score had a lower inflammatory score. Results from adjusted logistic regression showed reduction in the likelihood of “high-risk atherosclerosis” (defined as AIP ≥0.21) [intermediate: odds ratio (OR) = 0.90, 95% confidence interval (CI):0.85–0.95, ideal: OR = 0.81, 95%CI: 0.74–0.88] and “high CVD risk” (defined as CRP ≥3 mg/l) [intermediate: OR = 0.86, 95%CI:0.73–0.98, ideal: OR = 0.82, 95%CI:0.69–0.95] across the categories of CVH. Conclusions Our findings highlight that CVH metrics were associated with inflammatory score, SUA and AIP. Furthermore, participants with a better CVH score had a lower CVD risk. These results reinforce the importance of implementing healthy behaviours as proposed by the American Heart Association. If confirmed in clinical trials, this knowledge may have implications for CVD prevention and management. Keywords Cardiovascular healthC-reactive proteinAtherogenic index of plasmaSerum uric acid