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Review Article
Contribution of anthocyanin-rich foods in
obesity control through gut microbiota
interactions
Giovana Jamar
D
ebora Estadella
Luciana Pellegrini Pisani*
Department of Biosciences, Federal University of S~
ao Paulo – UNIFESP,
Santos, S~
ao Paulo, Brazil
Abstract
Obesity is characterized by low-grade inflammation and a
number of metabolic disorders. Distal gut microbes’ content
(microbiota) is not yet fully understood but evidence shows
that it is influenced by internal and external factors that modu-
late its composition and function. The evidence that gut micro-
biota composition can differ between healthy and obese
individuals, as well as for those who maintain specific dietary
habits, has led to the study of this environmental factor as a
key link between the pathophysiology of obesity and gut
microbiota. Data obtained about the role of anthocyanins
(ACNs) in microbiota may lead to different strategies to
manipulate bacterial populations and promote health. Antho-
cyanins have been identified as modulators of gut microbiota
that contribute to obesity control and these bioactive com-
pounds should be considered to have a prebiotic action. This
review addresses the relevance of knowledge about the influ-
ence of anthocyanins-rich food consumption on microbiota,
and their health-promoting potential in the pathophysiology of
obesity.
V
C2017 BioFactors, 00(00):000–000, 2017
Keywords: obesity; microbiota; anthocyanins; nutrition; diet
1. Introduction
Obesity is recognized as an inflammatory disease, and hyper-
trophy of the adipose tissue leads to metabolic and hemody-
namic dysfunction through the production of adipokines [1].
Changes in lifestyle and diet in the post-industrialized/wester-
nized era have been argued to contribute to the increasing
global incidence of obesity by altering the genetic composition
and metabolic activity of intestinal bacteria, thereby leading to
significant consequences in local and systemic health [2]. In
this context, there is increasing interest in understanding the
role of gut microbiota as an intermediary factor between
environmental and food behavior and its impact on the central
nervous system [3]. Microorganisms in the large intestine play
an important physiological role in vital processes such as
digestion, vitamin synthesis, and metabolism [4]. The complex
interaction between diet and gut microbiota may contribute to
an individual’s overall health and the incidence of chronic dis-
orders such as obesity [5]. Dietary composition, for example,
fatty acids, consumption of artificial sweeteners, and dietary
emulsifiers alters microbiota composition and can contribute
to inflammatory processes, weight gain, adiposity, and meta-
bolic disorders [6].
On the other hand, fruit and vegetable-based diets with anti-
oxidant, anti-inflammatory, anticarcinogenic, anti-adipogenic,
and antidiabetic activity, particularly anthocyanin (ACNs)-rich
diets, have been recommended to reduce the potential develop-
ment of chronic diseases. ACNs are flavonoids in fruits and vege-
tables that render them vivid red to blue in color and they are
abundant in the human diet. With more than 700 ACNs already
identified in nature, they are the primary polyphenols in berries,
such as blackcurrants, black elderberries, blackberries, bilber-
ries, whortleberries, blueberries, ac¸ai berries, and juc¸ara berries
[7–10]. ACN derivatives have differing aglycone (anthocyanidin,
i.e., cyanidin, delphinidin, malvidin, peonidin, pelargonidin, and
V
C2017 International Union of Biochemistry and Molecular Biology
Volume 00, Number 00, Month/Month 2017, Pages 00–00
*Address for correspondence: Luciana Pellegrini Pisani, Ph.D., Rua Silva
Jardim, 136, Vila Mathias, Santos, S~
ao Paulo, Brazil, C
odigo Postal: 11015-
020. Tel.: 155 13 38783700; Fax: 155 13 32232592; E-mail: lucianapi-
sani@gmail.com.
Received 23 December 2016; accepted 12 April 2017
DOI 10.1002/biof.1365
Published online 00 Month 2017 in Wiley Online Library
(wileyonlinelibrary.com)
BioFactors 1
petunidin) and glycone moieties (attaches to sugar residues, such
as glucose, xylose, galactose, arabinose, and rhamnose) [11].
There are also differences in the position and number of hydroxyl
groups, degree of methylation, and type and number of aliphatic
or aromatic acids (p-coumaric, caffeic, and ferulic acid) [12], with
cyanidin-3-glucoside (Cy-3-glu) being the most abundant ACN in
plants [11].
Because of their healthy biological effects, it has been
demonstrated that ACNs and their metabolites have preventive
properties against body fat accumulation [13] and are potent
modulators of inflammatory processes that seem to attenuate
the lipopolysaccharides (LPS)-induced nuclear factor-kappa B
(NF-jB) translocation to the nucleus cellular and mediate
inflammatory responses [14–16]. ACNs are associated with
beneficial changes in the gut microbiota as they might promote
intestinal colonization by specific groups of bacteria, particu-
larly Bifidobacterium spp., Lactobacillus spp., and Akkerman-
sia muciniphila [10,17–20]. These bacteria contribute to the
overall health of an individual as they participate in the activa-
tion and absorption of provitamins and phenolic compounds,
enhance gut barrier function, increase mucus secretion, and
modulate lipid metabolism and intestinal immune response
through cytokine stimulus [21,22]. These evidences confer a
prebiotic action to ACNs [10,23].
This review summarizes the current knowledge concerning
health benefits and obesity control characteristics associated
with the consumption of ACNs and microbiota interactions.
2. Anthocyanins and Gut Microbiota
Modulation
Different polyphenols have been suggested to affect the viabil-
ity of colonic bacterial groups, implying that dietary modula-
tion with polyphenols may play a role in reshaping the gut
microbial community and enhance host/microbe interaction to
provide beneficial effects such as weight loss [10]. There is
broad agreement that dietary polyphenols, in particular ACNs,
have the ability to modulate colonic bacteria growth [24],
which may play a role in the control of several parameters
involved in the development of metabolic diseases associated
with obesity [25].
Several studies have shown evidence of a wide range of
health-promoting characteristics of ACN-rich foods, including
protection against weight gain and metabolic disorders
observed with a high-fat diet [15,23,26,27]; reduction in the
risk of several chronic diseases, such as type 2 diabetes and
cardiovascular diseases [15]; improvement in lipid profiles,
inflammatory markers, and immunoregulatory cytokines; and
reduction in the membrane component of gram-negative bac-
teria, such as lipopolysaccharides (LPS) which induce NF-jB
transactivation in humans and animals [28–32].
To achieve these health benefits, ACN–gut microbiota
interactions should be considered to understand their biologi-
cal functions. The dichotomy between the biotransformation of
ACNs into a potentially more bioactive, low molecular weight
metabolite [33], and modulation of the gut microbiota compo-
sition by ACNs contributes to positive health outcomes [34].
ACNs have a low bioavailability, and it is estimated that
only 5%–10% of the total polyphenol intake is absorbed in the
small intestine [22]. The food matrix can also influence pheno-
lic compound bioavailability during digestion [35]. Moreover,
most dietary ACNs arrive intact at the colon and may interact
with the microbiota to be biotransformed and metabolized
before being absorbed across the intestinal mucosa [10]. This
interaction can involve hydrolysis, demethylation, reduction,
decarboxylation, dehydroxylation, or isomerization of these
compounds into simpler components that modulate absorption
and biological activity [33]. The first step in ACN bacterial
hydrolysis involves cleavage of the sugar moiety leading to the
formation of ACN aglycon, and the second phase includes
degradation into simple phenolic acids by the activities of two
bacterial enzymes, in particular a-L-rhamnosidase and b-D-
glucosidase, in the small intestine [36,37].
The degradation of phenolic acids by enteric bacterial or
chemical conversions may produce other metabolites, includ-
ing protocatechuic acid, syringic acid, vanillic acid, phloroglu-
cinol aldehyde, phloroglucinol acid, and gallic acid [31,37].
These acidic metabolites are probably absorbed through
monocarboxylic acids transported by epithelial cells [10]. The
low level of oxygen in the small and particularly, the large
intestine should also be considered because low oxygen may
protect the ACN structure. The concentration of bacteria in the
small intestine can be expected to increase distally, thus
increasing the susceptibility of microbial-mediated catabolism
of ACNs [38].
It is considered that gut microbiota can increase the bioa-
vailability of the phenolic content of food and quadruple its
antioxidant activity [22,39]. ACNs and metabolites concur-
rently formed in the intestine have the ability to promote and
inhibit the growth of bacterial groups [18]. ACNs can exert an
antimicrobial activity with inhibitory effects on the growth of a
wide range of human pathogenic bacteria, both gram-negative
(Citrobacter freundii,Escherichia coli,Pseudomonas aerugi-
nosa, and Salmonella enterica ser. typhimurium) and gram-
positive (Listeria monocytogenes,Staphylococcus aureus,
Bacillus subtilis, and Enterococcus faecalis). Mechanisms
underlying ACN activity include both membrane and intracel-
lular interactions of these compounds [40], such as inducing
the release of LPS molecules from the outer membrane of
gram-negative bacteria [10].
ACNs are generally active by different microbes; however,
gram-positive bacteria are usually more susceptible to the
action of ACNs than gram-negative bacteria [41]. Nonetheless,
only a few bacterial genera (e.g., Bifidobacterium,Lactobacil-
lus,Akkermansia,Bacteroides, and Eubacterium), which cata-
lyze the metabolism of phenolics, have been described as con-
tributing to the health benefits of the host [20,41].
An increase in Bifidobacterium is favored in the presence
of carbohydrates, non-digestible carbohydrates, and ACNs
BioFactors
2Anthocyanin-Rich Foods in Obesity Control
[42], and it is recognized as one of the most important bacte-
rial groups associated with human health [19]. Among its ben-
efits, studies have reported anti-obesity effects [43] and choles-
terol regulation [44]. An increase in the expression of zonula
occludens-1 (ZO-1) has also been reported [45]; ZO-1 is a
peripheral membrane protein involved in the regulation of
paracellular permeability that is associated with a complex of
proteins localized at the apical side of epithelial cell mem-
branes–claudin and occludin–that form a tight junction barrier
in the lumen against microorganisms and food antigens [46].
Studies have already shown a role of ACNs in the bifido-
genic effect by a reduction in inflammatory markers and bene-
ficial changes in gut microbiota by competition for a growth
substrate in vitro [47], in humans [48], and in animals [49].
Previous data by our research group using a metabolic
programming model revealed that supplementing the diet of
pregnant rats with juc¸ara berries (262.4 mg ACN/100 g fresh
matter) reduced metabolic and inflammatory markers and
increased Lactobacillus and Bifidobacterium spp. expression of
genomic DNA and ZO-1 gene in their offspring, demonstrating
that phenolic compounds present in this fruit contribute to the
control of inflammation and prevention of the development of
chronic diseases through the intestinal pathway up until adult-
hood [50,51].
Recently, Guergoletto et al. [52] reported the potential pre-
biotic effect of juc¸ara berries by modulating the colonic micro-
biome in vitro. They found that it promoted bifidogenic effects,
including the antimicrobial effect on pathogenic microorgan-
isms by increasing the production of short-chain fatty acids
(SCFAs), acetate, and propionate.
The dietary administration of dealcoholized red wine
extract for 16 weeks to rats changed their intestinal micro-
biota populations from a predominance of Bacteroides,Clos-
tridium, and Propionibacterium spp. to a predominance of Lac-
tobacillus,Bifidobacterium spp., and Bacteroides, showing that
the role of ACNs in intestinal modulation favors an increase in
beneficial bacteria [42].
Supplementing diet-induced obese mice with cranberry
and grape extracts resulted in lower intestinal and systemic
inflammation, improved metabolic features, and increased the
abundance of A.muciniphila in their gut microbiota with a
prebiotic effect [20,53]. A.muciniphila inhabits the mucus
layer and is one of the most abundant members of the human
gut microbiota, comprising between 1% and 5% of our intesti-
nal microbes [20]. It is associated with increased mucus layer
thickness, improved glucose homeostasis, alleviated metabolic
endotoxemia, and improved cardiometabolic parameters in
obese individuals undergoing caloric restriction [20,54]. Cur-
rently, A.muciniphila has been considered as a therapeutic
option to target human obesity and associated disorders [54].
Recently, several studies have considered ACN benefits
after degradation by colonic microbiota. These metabolites
may contribute to the bioavailability of ACNs [37] and may be
responsible for antioxidant [55] and protective effects as nitric
oxide production increases [56]; they inhibit angiotensin-
converting enzymes to improve blood pressure [47]; minimize
weight gain and improve glucose metabolism [31]; improve the
plasma lipid profile and inflammation [57]; positively modulate
the intestinal bacterial population by enhancing the growth of
Bifidobacterium spp., Lactobacillus spp., and Enterococcus
spp.; and reduce Clostridium histolyticum, a potentially harm-
ful bacterium [47].
Therefore, there is a broad consensus that ACNs have pre-
biotic effects similar to the modulation of gut microbiota com-
position [18,24]. This benefits bacteria that are linked to
reducing LPS levels [57] and selective antimicrobial activities
against pathogenic gut bacteria [22] (Fig. 1), contributing to
chronic disease control even though the mechanisms have not
yet been elucidated [57].
3. Anthocyanins in Obesity and
Interplay with Gut Microbiota
The Western diet has altered the genetic composition and met-
abolic activity of our resident microorganisms (the human gut
microbiome). Such diet-induced changes in gut-associated
microbial communities are now suspected of contributing to
growing epidemics of chronic disease, including obesity, in the
developed world [58].
Normal weight and obese individuals have a different
microbiota composition. Emerging data have suggested that
obese individuals have a higher ratio Firmicutes/Bacteroidetes
than normal weight controls. Moreover, when they lose
weight, Firmicutes abundance decreases and becomes more
similar to that in lean subjects [59], reinforcing the hypothesis
that specific bacteria genera and species participate in the
regulation of energy homeostasis, modulation of energy bal-
ance, expansion of the adipose tissue, and glucose metabolism,
leading to a chronic inflammatory state [60–64] (Fig. 2).
Although different therapies have been suggested to
attenuate obesity including appetite or food control, chemically
manufactured medicines, different herbal drugs, and physical
exercise, obesity management remains a critical issue because
of its drastic outcomes. ACNs are valuable compounds that
play an important role in maintaining human health as they
can be used prophylactically and therapeutically owing to sev-
eral properties [11,13,65]. Besides that, ACNs can normalize
the ratio between beneficial and pathogenic bacteria and
plasma endotoxemia and reduce the impact of a high-fat diet
on the host’s metabolism [66]. Early reports suggested that
antioxidant properties alone are responsible for ACNs health-
promoting effects; however, it is now appreciated that ACNs
act beyond their antioxidant properties and likely influence an
array of cell signaling, anti-inflammatory, and gene expression
pathways [39].
ACNs have been shown to exert different degrees of anti-
oxidant and anti-inflammatory activities, depending on their
chemical structure [12]; therefore, the effects of diverse ACN-
rich berries have been tested. Recently, a study on three
Jamar et al. 3
prospective human cohorts demonstrated that a higher intake
of flavonoid-rich foods, mainly ACNs, may contribute to weight
maintenance in adulthood and may help in refining dietary
recommendations for the prevention of obesity and its poten-
tial consequences [67].
Basu et al. [68] found that ingestion of 742 mg of blue-
berry ACNs for 8 weeks significantly improved blood pressure
and oxidized low-density lipoprotein (LDL)-cholesterol levels,
whereas blood glucose levels, body weight, and waist circum-
ference were not improved in obese individuals. Similarly,
other researchers have not shown alterations in body weight
gain and white adipose tissue weight in mice fed a high-fat
diet after the ingestion of blueberry juice (1887 mg/mL ACN) in
place of drinking water over a period of 72 days [65]. How-
ever, consumption of high doses (200 mg/kg) of blueberry
ACNs by high-fat diet induced obese male mice over 8 weeks
reduced their body weight by 19.4%; decreased serum glucose
levels; attenuated epididymal tissue; improved lipid profiles;
and significantly down-regulated tumor necrosis factor alfa
(TNFa), interleukin 6, peroxisome proliferator-activated recep-
tors (PPARc), and fatty acid synthesis (FAS) gene expression
levels [69].
These studies highlight the potential of ACNs in weight
control and/or metabolic disorders related to overweight. How-
ever, the results depend of the dose and species of fruit or
compound administered. Nonetheless, how microbial pathways
influence weight gain and how ACNs affect obesity remains
uncertain. Next, we summarize the mechanisms involved in
the relationship between gut microbiota and obesity and ACNs
role in these processes.
The potential prebiotic effect of anthocyanins on gut microbiota and obesity. SCFA: short-chain fatty acids; FIAF: fasting-
induced adipose factor; LPS: lipopolysaccharide; ZO-1: zonula occludens-1; IR: insulin resistance. Anthocyanins and metabolites
formed in the intestine change the composition of the gut microbiota. This is associated with restored tight-junction protein
(ZO-1 and Occludin) distribution and localization. Hence, the gut permeability is decreased and plasma lipopolysaccharide
(LPS) levels (metabolic endotoxemia) are lowered, improving low-grade inflammation and obesity-related comorbidities. Antho-
cyanins decrease the activity of transcription factor NF-jB in the cell nucleus by decreasing gene expression of inflammatory
cytokines; exerting its anti-inflammatory action. Anthocyanins have the ability to promote the growth of Bifidobacterium spp.,
which increases the intestinal production of FIAF that inhibits fat storage in the host. Bifidobacterium spp. degrades SCFA; pro-
pionate stimulates mucus secretion and contributes to thickening of the mucus layer. While reduced mucus layer thickness
favors microbiota encroachment.
FIG 1
BioFactors
4Anthocyanin-Rich Foods in Obesity Control
3.1. Lipogenesis
The mechanisms of the apparent weight gain implied an
increase in the intestinal glucose absorption, energy extraction
from non-digestible food component, and concomitant higher
glycemia and insulinemia, two key metabolic factors regulating
lipogenesis [70]. Moreover, glucose and insulin are also known
to promote hepatic de novo lipogenesis by the expression of sev-
eral key enzymes, such as acetyl-CoA carboxylase (ACC) and
fatty acid synthase (FAS), which are controlled by carbohydrate-
responsive element-binding protein (ChREBP) and sterol-
responsive element-binding protein (SREBP-1) [71]. Germ-free
mice exhibited decreased hepatic ChREBP and SREBP-1 mRNA
levels by modulation of lipogenesis by energy extraction from
SCFAs [72]. These data provide evidence that the digestion of
polysaccharides by microbial enzymes and increase in saccha-
ride delivery to the liver participate in higher lipogenesis.
ACNs can reduce the expression of PPARc, FAS, and
ChREBP [69,73], and differentiation of preadipocytes from the
Dietary contribution in changes in gut microbiota, fat storage, and development of metabolic disorders via LPS-induced. SCFA:
short-chain fatty acids; ACC: acetyl-CoA carboxylase; FAS: fatty acid synthase (FAS); ChREBP: Carbohydrate responsive
element-binding protein; SREBP-1: Sterol responsive element-binding protein; FIAF: fasting-induced adipose factor; LPL: lipo-
protein lipase; LPS: lipopolysaccharide; TLR-4: toll like receptor 4; GLP-1: glucagon-like peptide-1; PYY: peptide YY. Gut micro-
biota might be involved in energy storage. Environmental factor such as gut microbiota may regulate energy storage by
providing lipogenic substrates (SCFA, monosaccharides) to the liver, increasing hepatic lipogenesis and/or by suppressing the
FIAF in the gut, which increase LPL. It contributes to the release of fatty acids and triacylglycerol from circulating lipoproteins
in adipose tissue. Consumption of the Western diet (high in saturated/trans fat and simple sugars and low in fibers) is one of
the leading causes of obesity worldwide. Obesity-linked dysbiosis is associated with disrupted intestinal barrier. Western diet
causes changes in gut microbiota by specifically decreases Bifidobacterium spp. It is associated with a higher gut permeability
leading to higher plasma LPS levels (metabolic endotoxemia) that promotes low-grade inflammation-induced metabolic disor-
ders (insulin resistance, diabetes, obesity, steatosis, adipose tissue macrophages infiltration). Prebiotics increase Bifidobacte-
rium spp., decrease plasma LPS levels and normalized low-grade inflammation (decreased endotoxemia and proinflammatory
cytokines). This modulation is associated with changes in the plasma gut peptides levels (enhanced GLP-1 and PYY, and
reduced ghrelin). These effects are associated with satiety, weight loss, increase in insulin sensitivity, reduction in fat mass,
and low-grade inflammation characterizing obesity.
FIG 2
Jamar et al. 5
subcutaneous and visceral adipose tissue, suggesting inhibitory
effects on adipogenesis in the white adipose tissue. Recently,
You et al. [74] demonstrated that Cy-3-glu may act in brown
adipogenesis increasing the number of mitochondria.
Ac¸ai seed extract reduces lipogenesis and glucose levels
because of reduced expressions of SREBP-1c and the enzyme
HMG-CoA reductase and increased expressions of AMP-
activated protein kinase (AMPK) in mice that were fed a high-
fat diet [8]. AMPK plays an important role in the regulation of
fatty acids and glucose metabolism, favoring weight control as
well as appetite regulation. The activity of this enzyme is ana-
bolic when inhibited, blocking catabolic processes. The diver-
sity of the microorganisms in the gut can suppress fatty acid
oxidation in the muscle via mechanisms involving inhibition of
AMPK and favor adiposity and insulin resistance [71,75].
The activation of AMPK and fasting-induced adipose factor
(FIAF) lead to an inhibition of lipoprotein lipase (LPL), an
enzyme that regulates triacylglycerol metabolism and that can
be modulated by the microbiota [72]. FIAF participation in
lipid metabolism was reinforced when it was shown that
germ-free FIAF
2/2
mice were not protected from diet-induced
obesity and they demonstrated increased weight gain, intra-
abdominal adiposity, and higher leptin and insulin levels,
despite similar food intake, comparing with FIAF
1/1
mice [75].
This set of experiments demonstrated, for the first time, that
an environmental factor, such as gut microbiota, may regulate
energy storage [71].
A new insight demonstrated that gut microbiota plays an
unexpectedly important role in post-dieting weight regain, and
it could have been avoided or treated by altering microbiome
function or composition. In addition, flavonoid-based “post-
biotic” intervention ameliorates excessive secondary weight
gain. The possible mechanism for this action is that flavonoids
impact energy expenditure by induction of the major thermo-
genic factor uncoupling protein-1 in the brown adipose
tissue [76].
These evidences indicate a beneficial role of dietary ACNs
in preventing weight gain. The underlying mechanisms have
been hypothesized to involve factors including, but not
restricted to, suppression of fat absorption from the gut, adipo-
cyte differentiation, fatty oxidation, and sympathetic activation
of thermogenesis [77].
3.2. Energy Homeostasis Mechanism
The energy balance is regulated via neuronal and hormonal
signals. There is equilibrium between orexigenic and anorexi-
genic neuropeptides in the hypothalamus and brain stem to
regulate food intake, body weight, and energy homeostasis. In
obesity, there is a complex disorder involving an imbalance in
orexigenic and anorexigenic circuits and stimulation of the
intracellular neuropeptide Y (NPY), which further effects food
intake and lipid accumulation [78]. Neurons of the arcuate
nucleus that produce NPY exhibit enhanced expression of
gamma-aminobutyric acid (GABA), a G-protein coupled recep-
tor (GPR) and main inhibitory neurotransmitter in the central
nervous system. Thus, GABA can inhibit a tonic restraint to
elicit a feeding response directly or in conjunction with NPY
and other orexigenic signals [79].
Recently, Badshah et al. [78] demonstrated an efficient
anti-obesity capacity of black soybean ACNs via regulating the
expression of NPY and GABA in the hypothalamus. The exact
mechanism underlying these modifications by this ACNs treat-
ment is unclear. However, GABA may be an intermediate
influence on the microbiota in the gut–brain axis. It is located
throughout the gastrointestinal tract and is found in enteric
nerves as well as in endocrine-like cells, implicating GABA as
both a neurotransmitter and an endocrine mediator influenc-
ing gastrointestinal function. Experimental fecal extraction
studies revealed that GABA was increased following Roux-en-
Y gastric bypass surgery and that it could have been derived
from the microbial processing of putrescine [80,81]. Increased
expression of fecal GABA is consistent with the well-defined
increase of glucagon-like peptide 1 (GLP-1), an anorexigenic
gut hormone. Furthermore, ACNs may induce GLP-1 secretion
and contribute to energy homeostasis [82].
The activation of GLP-1 receptors, mainly GPR43 and 41
(also called free fatty acid receptors 2 and 3, respectively),
induce the secretion of peptide YY (PYY) and leptin, hormones
that influence intestinal function and appetite regulation by
inhibiting orexigenic neurons of the arcuate nucleus [43–45].
PYY favors the reduction of gut motility and increased energy
harvest from the diet, in particular SCFAs, which are sub-
strates for hepatic lipogenesis. Therefore, gut microbiota may
interfere with the central nervous system based on the pres-
ence or absence GPR41, thereby influencing the central regu-
lation of appetite and satiety [45] through the modulation of
PYY and SCFA absorption [43,44].
Access to the central nervous system is tightly controlled
by the blood–brain barrier (BBB); it is likely that a small and
specific set of bacterial metabolites modulate brain morphol-
ogy. The gut microbiota is also crucially involved in modulat-
ing BBB [83] as germ-free mice have a more permeable BBB
than conventional mice [84]. ACN gut microbiota metabolites
can cross BBB and be allocated to various brain regions, sug-
gesting that these compounds may deliver their antioxidants
and centrally signal and modify capabilities [85,86], although
the mechanisms remain unclear. However, it is worth high-
lighting that ACNs have a prebiotic effect that contributes to
the modulation of gut peptides, inducing effects on satiety and
food intake [87].
3.3 Obesity Inflammation Pathway
Obesity is characterized by the massive expansion of adipose tissues
and is associated with inflammatory complications. LPS was identi-
fiedasatriggerfactorfortheearly development of inflammation
and metabolic diseases. High LPS levels form a complex containing
LPS-binding proteins and the CD14 co-receptor that is recognized
by Toll-like receptor 4, a transmembrane receptors, triggering an
inflammatory response through the complex signaling pathways
BioFactors
6Anthocyanin-Rich Foods in Obesity Control
with NF-jB activation and the subsequent expression of pro-
inflammatory cytokines [60].
The activated NF-jB pathway may also impair insulin sig-
naling, which can lead to insulin resistance. LPS has been
found at a significantly higher level in the serum of obese than
lean individuals, and it is associated with a high-fat diet, par-
ticularly containing saturated fatty acids [6,88,89]. It creates a
metabolic endotoxemia that causes alterations in bacterial
diversity and microbiota balance (dysbiosis), damage to the
mucosal integrity, and dramatically increases intestinal per-
meability, reducing the expression of epithelial tight junction
proteins [60,88,90]. It is even questionable as to whether LPS
induces weight gain or only enhances subclinical inflammation
and contributes to metabolic changes, such as insulin resist-
ance, regardless of adiposity induction [88].
Changes in the number and size of adipocytes affect the
microenvironment of expanded fat tissues and are accompa-
nied by alterations in adipokine secretion, adipocyte death,
local hypoxia, and fatty acid fluxes. Chronic over-nutrition trig-
gers uncontrolled inflammatory responses, leading to systemic
low-grade inflammation and metabolic disorders, such as insu-
lin resistance [91].
ACNs act on the adipose tissue, inducing changes in adipo-
kine expression levels, as adiponectin, which enhances insulin
sensitivity, in rat [92] and human adipocytes [93]. Adiponectin
also lowers muscle triglyceride levels by increasing the influx
and combustion of free fatty acids resulting in decreased
hepatic level of triglycerides [65]. It has recently been reported
that a diet supplemented with wild blueberry powder signifi-
cantly increased blood adiponectin levels and decreased
inflammatory marker levels in the white adipose tissue [94],
including those related to cardiovascular risk (C-reactive pro-
tein (CRP), interleukins, TNFa, and Vascular cell adhesion pro-
tein 1 (VCAM-1)) [95]; decreased NF-jB activity [96] and serum
LPS levels [97]; and ameliorated dyslipidemia [98], showing
the anti-inflammatory effects of the different ACNs present in
the fruit [31].
4. Concluding Remarks and Future
Perspectives
ACNs seem to have an anti-obesity effect with properties that
prevent body fat accumulation, insulin resistance, dyslipide-
mia, and inflammation while contributing to energy homeosta-
sis and satiety. The exact molecular mechanism of their anti-
obesity effects should be clarified; their benefits may be linked
to ACN microbiota modulation.
There is an insufficient understanding about the difference
in ACN metabolism and biotransformation in the gastrointesti-
nal tract of normal weight versus obese individuals as well as
the role of intact versus disrupted gut microbiomes in these
processes.
The literature shows that a wide variety of results and
techniques were employed in the studies, such as different
ACN sources and the biotransformation of ACNs in either a
food matrix or isolated. This makes it difficult to understand
the exact mechanism of each individual compound. Neverthe-
less, there is broad agreement that ACNs have health-
promoting effects, have the ability to modulate colonic bacte-
rial growth, improve chronic low-grade inflammation, and
may indeed exert a prebiotic activity. It is crucial to emphasize
the benefits for bioavailability and/or bioactivity from ACN
metabolites that are synthesized by colonic microbiota.
Thus, microbiota modulation through dietary interventions
with ACN-rich foods may offer new directions for the preven-
tion and/or treatment of obesity. Future studies are still
required to understand these mechanisms and to be able to
specifically understand the interaction between the type of
bacteria and different metabolites derived from the degrada-
tion of ACNs.
Conflicts of Interest
There is no conflict interest.
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BioFactors
10 Anthocyanin-Rich Foods in Obesity Control
