Available via license: CC BY-NC-ND 4.0
Content may be subject to copyright.
Functional Foods in Health and Disease 2015; 5(6):200-208 Page 200 of 208
Research Article Open Access
The effect of extracts of Irvingia gabonensis (IGOB131) and Dichrostachys
glomerata (Dyglomera™) on body weight and lipid parameters of healthy
overweight participants
Boris Azantsa,1,3 Dieudonne Kuate,2 Raoul Chakokam,3 Ghislain Paka,3 Barbara
Bartholomew4 and Robert Nash4*
1Department of Biochemistry and Molecular Biology, Faculty of Science, University of Buea,
SW Region, Cameroon; 2Program in Nutrition, School of Health Sciences Universiti Sains
Malaysia, 16150 Kubang Kerian Kelantan, Malaysia; 3Department of Biochemistry, Faculty of
Science, BP 812, University of Yaounde 1, Yaounde, Cameroon; 4PhytoQuest Limited, Plas
Gogerddan, Aberystwyth, Ceredigion SY23 3EB, UK
*Corresponding author: Robert Nash, PhD, PhytoQuest Limited, Plas Gogerddan,
Aberystwyth, Ceredigion SY23 3EB, UK
Submission Date: April 4, 2015, Acceptance date: June 6, 2015: Publication date: June 9, 2015
Running Title: IGOB131 and Dyglomera™ in weight management
ABSTRACT
Background: Previous work reported the benefits of extracts of 2 Cameroonian spices – Irvingia
gabonensis and Dichrostachys glomerata— on obese people with metabolic syndrome.
Considering the physio-metabolic changes that accompany obesity, the present study investigates
the effects of these extracts on healthy overweight participants over an 8-week test period.
Methods: The study was an 8 week randomized double-blind, placebo controlled design
involving 48 overweight (BMI 26 – 30) participants (27 females and 19 males), divided into 3
groups – placebo, 300 mg I. gabonensis extract (IGOB131), or 300 mg D. glomerata extract
(DyglomeraTM). Capsules containing the placebo or the test formulations were administered once
daily before the main meal of the day. No major dietary changes or changes in physical activity
were demonstrated during the study. Weight and blood lipid parameters were measured at
baseline, and at the 4 and 8 weeks interval.
Results: Compared to the placebo group, there were significant (p<0.05) reductions in weight of
participants in both test groups over the 8 week period. However, these significant changes were
not observed in the initial 4 weeks, even though the lipid parameters in the test groups changed
significantly (p<0.05).
Functional Foods in Health and Disease 2015; 5(6):200-208 Page 201 of 208
Conclusion: The extracts of Irvingia gabonensis and Dichrostachys glomerata, at a dose of 300
mg per day, were effective in reducing weight and positively modifying lipid parameters in
healthy overweight participants.
Keywords: Overweight, Dichrostachys, Irvingia, waist-hip circumference, blood lipids.
INTRODUCTION
Obesity is a multifaceted disease which generally leads to several complications and increased
morbidity and mortality related to coronary heart diseases, diabetes type 2, metabolic syndrome,
stroke and cancers [1, 2]. To become obese, healthy individuals generally experience progression
from normal weight, to being overweight (considered generally as being healthy), and finally to
obese (considered as being an unhealthy or diseased state). Treatment or management of obesity
is difficult, due the complexity of associated complications. Therefore, attempts to prevent
progression in body weight and fat accumulation, from an overweight/pre-obese condition to
obesity, can lower worldwide mortality rates related to obesity. This study investigates the
effects of the extracts of Irvingia gabonensis (IGOB131) and Dichrostachys glomerata
(DyglomeraTM) on healthy overweight participants over an 8-week test period.
PARTICIPANTS AND METHODS
A total of 48 overweight participants aged between 23 and 55 years were selected from a group
of 220 overweight and obese persons responding to a radio advertisement in Yaoundé,
Cameroon. After physical examination and laboratory screening tests, diabetics, pregnant and
lactating women were excluded. All participants were judged as healthy (normal range of
temperature, no clinical consultation within the previous 2 weeks) by the resident physician, and
were not on any weight reducing protocol. The purpose, nature and potential risks of the study
were explained to all patients and a written informed consent was obtained before their
participation. The local research ethics committee approved the experimental protocol.
Study design: Participants were given one of three different types of capsules containing either
300mg of Irvingia gabonensis extract (IGOB131, with ≥7% albumin and ≥1% ellagic acid), 300
mg of hydroethanolic (90:10, water :ethanol) extract of Dichrostachys glomerata
(Dyglomera™) or oat bran (placebo). The capsules were taken one-half hour before the main
meal with a glass of warm water. Capsules were identical in shape, colour, and appearance, with
neither participant nor researchers knowing what capsule they received. During the 8 week
experimental period, participants were examined weekly, with their body weight, body fat, waist
and hip circumferences recorded each time. Subjective findings, such as increased or decreased
appetite, feeling of lightness and gastrointestinal pains, were individually noted. The participants
were also interviewed about their physical activity and food intake during the trial, and were
instructed not to modify these habits.
Anthropometric measurements: The heights of participants were measured during the first
visit and their weights at each subsequent visit. BMI was also calculated, and served as a basis of
inclusion or exclusion in the study. The percent body fat was measured with a Tanita™ BC-418
Functional Foods in Health and Disease 2015; 5(6):200-208 Page 202 of 208
Body Composition Analyzer/Scale, while waist and hip circumferences were measured with a
soft non-stretchable plastic tape. In an effort to ensure intra-individual consistency, the
participants were measured at approximately the same time of the day for each visit.
Laboratory methods: Blood samples were collected after a 12h overnight fast into heparinized
tubes at the beginning of the study, after four weeks, and at the end (8 weeks) of treatment. The
concentrations of total cholesterol, triacylglycerol, HDL-cholesterol, in plasma were measured
using a commercial diagnostic kit (Cholesterol infinity, triglycerides Int, EZ HDLTM cholesterol
from SIGMA Diagnostics. LDL_cholesterol values were calculated using the Friedwald equation.
Statistical Analysis: Results are expressed as mean SEM. Paired Student’s t-test was used on
the start and end values of placebo and test capsules, and also on the differences between the
placebo and test groups. In the tables in the same row, values with different letters (a, b) are
significantly different at p < 0.05 and p <0.01 respectively.
RESULTS
There were 3 dropouts, two of whom relocated to a different town, and the third, who gave no
specific reason. No adverse side effects were reported.
Effect of IGOB131 and Dyglomera™ on Body weight
Overweight participants who received either IGOB131 or Dyglomera (300mg daily) for 8 weeks
had significantly (p<0.05) greater reduction in body weight compared to those on placebo (Table
1a). This reduction in body weight corresponded to a 9-10% reduction in BMI (Table 1b).
Table 1 a: The effect of IGOB131 and Dyglomera™ on body weight (kg)
T0
T4
T8
Variation (%)
Placebo
73.51 ± 1.08a
72.76 ± 1.28a
72.26 ± 1.25a
-1.74 ± 0.38a
Test IGOB
74.07 ± 0.85a
70.25 ± 0.90a
66.66 ± 0.89b
-10.00 ± 0.58b
Test Dyglo
70.56 ± 0.83a
67.42 ± 1.19b
64.28 ± 1.09b
-8.92 ± 0.80b
Values are means ± sem
There was a slight but insignificant decrease in weight and BMI for participants taking placebo
over the 8 -week test period.
Table 1b: The effect of IGOB131 and Dyglomera™ on BMI (kg/m2)
T0
T4
T8
Variation (%)
Placebo
27.58 ± 0.60a
27.27 ± 0.56a
27.08 ± 0.59a
-1.74 ± 0.38a
Test IGOB
27.31 ± 0.51a
25.89 ± 0.48a
24.58 ± 0.48b
-10.00 ± 0.58b
Test Dyglo
26.67 ± 1.84a
25.45 ± 0.50b
24.30 ± 0.63b
-8.92 ± 0.80b
Values are means ± sem
Body weight, BMI, % body fat, and waist-to- hip circumferences were slightly (1.3%, 0.8
cm, 2.0 cm respectively) reduced in the placebo group over the 8 week trial period. However,
Functional Foods in Health and Disease 2015; 5(6):200-208 Page 203 of 208
IGOB131, as well as Dyglomera™, brought about a more significant reduction in these
parameters (Tables 1c, 1d and 1e).
Table 1c: The effect of IGOB131 and Dyglomera™ on body fat (%)
T0
T4
T8
Variation (%)
Placebo
37.4 ± 2.4a
37.2 ± 1.5a
36.1 ± 1.6a
-1.3 ± 0.2a
Test IGOB
36.8 ± 1.4a
34.9 ± 2.3b
31.7 ± 1.8b
-5.1 ± 0.3b
Test Dyglo
37.6 ± 2.8a
35.3 ± 1.5b
32.3 ± 1.5b
-5.3 ± 0.5b
Values are means ± sem.
Table 1d: The effect of IGOB131 and Dyglomera™ on waist circumference (cm)
T0
T4
T8
Variation (%)
Placebo
87.6 ± 2.5a
87.2 ± 1.7a
86.8 ± 1.8a
-0.8 ± 0.3a
Test IGOB
86.3 ± 2.3a
84.9 ± 2.3a
83.2 ± 1.6b
-3.1 ± 0.3b
Test Dyglo
86.8 ± 1.8a
85.1 ± 1.6b
83.1 ± 1.3b
-3.7 ± 0.6b
Values are means ± sem.
Table 1e: The effect of IGOB131 and Dyglomera™ on hip circumference (cm)
T0
T4
T8
Variation (%)
Placebo
92.8 ± 2.6a
91.7 ± 2.4a
90.8 ± 2.3a
-2.0 ± 0.4a
Test IGOB
91.6 ± 3.1a
87.8 ± 3.3a
85.3 ± 2.8b
-6.3 ± 1.2b
Test Dyglo
92.7 ± 2.4a
90.3 ± 2.5b
88.4 ± 0.6b
-4.3 ± 1.3b
Values are means ± sem.
Effect of IGOB131 and Dyglomera™ on Blood lipids
Eight-week use of IGOB131 by overweight participants reduced plasma total cholesterol by
10.5%, LDL-cholesterol by 24.7%, and triacylglycerol by 12.2%. This treatment also increased
the concentration of HDL-cholesterol by 12.1% (Tables 2, 3, 4). A similar change in these
parameters was observed in the Dyglomera™ group; 8.45% for total cholesterol, 17.27% for
LDL-cholesterol and 14.30% for triglycerides. There was also a 13.36% increase in HDL-
cholesterol.
Table 2: The effect of IGOB131 and Dyglomera™ on total cholesterol (mg/dL)
T0
T4
T8
Variation (%)
Placebo
187.81 ± 2.75a
186.28 ± 3.04a
183.13 ± 2.82a
-2.20 ± 0.36a
Test IGOB
186.53 ± 2.63a
174.64 ± 2.48b
166.76 ± 2.42b
-10.50 ± 0.85b
Test Dyglo
190.72 ± 2.47a
181.09 ± 2.65a
174.56 ± 3.13a
-8.45 ± 1.32b
Values are means ± sem.
Table 3: The effect of IGOB131 and Dyglomera™ on triglycerides (mg/dL)
Functional Foods in Health and Disease 2015; 5(6):200-208 Page 204 of 208
T0
T4
T8
Variation (%)
Placebo
61.94 ± 2.41a
59.76 ± 2.16a
58.19 ± 2.82a
-5.75 ± 1.57a
Test IGOB
56.55 ± 2.42a
52.00 ± 2.06b
49.53 ± 2.08b
-12.20 ± 1.13b
Test Dyglo
58.63 ± 2.52a
52.76 ± 1.98b
50.40 ± 1.74b
-14.30 ± 1.55b
Values are means ± sem.
Table 4: The effect of IGOB131 and Dyglomera™ on LDL-cholesterol (mg/dL)
T0
T4
T8
Variation (%)
Placebo
108.64 ± 2.78a
107.30 ± 3.16a
103.40 ± 2.82a
-4.85 ± 0.87a
Test IGOB
106.40 ± 3.29a
90.45 ± 3.10b
80.05 ± 2.97b
-24.76 ± 1.29b
Test Dyglo
123.00 ± 4.04b
110.76 ± 2.84a
101.43 ± 3.04a
-17.27 ± 1.82b
Values are means ± sem.
Over the 8-week test period, the circulating levels of HDL-cholesterol were also significantly
increased (p<0.05) by Dyglomera™, as well as IGOB131 (Table 5).
Table 5: The effect of IGOB131 and Dyglomera™ on HDL-cholesterol (mg/dL)
T0
T4
T8
Variation (%)
Placebo
66.78 ± 1.38a
67.02 ± 1.48a
68.09 ± 1.45a
1.98 ± 0.69a
Test IGOB
68.81 ± 1.12a
73.79 ± 1.00b
76.80 ± 0.81b
12.06 ± 1.59b
Test Dyglo
65.52 ± 2.08a
70.47 ± 3.05b
74.25 ± 2.53b
13.36 ± 2.26b
Values are means ± sem.
DISCUSSION
Results demonstrated that the extracts at a dose of 300 mg per day, were effective in significantly
reducing weight, BMI, body fat, waist circumference, and hip circumference. IGOB131 and
DyglomeraTM also positively modified lipid parameters in healthy overweight participants. These
findings are superior to the majority of other randomized double-blind placebo-controlled
clinical trials evaluating medicinal plant extracts, herbs and spices. For example, recently, an 8-
week study carried out on 78 overweight subjects with Cuminum cyminum L. and Orlistat 120,
showed significant decreases in weight (-1.1 ± 1.2 and -0.9 ± 1.5 vs. 0.2 ± 1.5 kg, respectively, p
= 0.002) and BMI (-0.4 ± 0.5 and -0.4 ± 0.6 vs. 0.1 ± 0.6 kg/m2, respectively, p = 0.003), in
addition to beneficial effects on insulin metabolism compared with placebo [3]. Comparing those
results to our study, the reduction in weight observed is nine times higher with IGOB131 and
eight times higher with DyglomeraTM than C. cyminum. IGOB131 and DyglomeraTM reduced
BMI 25 times and 22 times respectively, more effective than C. cyminum in overweight subjects
and maintaining participants within a healthy BMI bracket.
The activity of plant extracts can be explained through the action some of their components
have on body-fat metabolism and oxidation or increasing metabolic rate [1]. This has been
Functional Foods in Health and Disease 2015; 5(6):200-208 Page 205 of 208
demonstrated in trials with epigallocatechin-3-gallate of green tea, virgin olive oil, and Lycium
barbarum causing higher fat oxidation in human. The compounds may act by activating lipid
metabolism, acceleration of oxidation, suppression of fatty acid synthesis and PPARc agonistic
activity in overweight individuals, as well as in obese patients.
IGOB131 and DyglomeraTM have previously proven their activities with overweight and/or
obese volunteers (defined as BMI > 25 kg/m2). In a previous study [4] on 102 healthy
overweight and obese participants who were administered a dose of 150 mg twice daily before
meals, there were significant improvements in body weight, body fat, and waist circumference,
as well as plasma total cholesterol, LDL cholesterol, blood glucose, C-reactive protein,
adiponectin and leptin levels compared to a placebo group. IGOB131 was also very active in
overweight participants in this study. In both obese and overweight groups, IGOB131 activity
was attributed to the ability of the extracts to favorably impact adipogenesis through a variety of
critical metabolic pathways, including PPAR gamma, leptin, adiponectin, and glycerol-3
phosphate dehydrogenase [5]. Furthermore, compared to the placebo group, the obese group
treated with Dyglomera™ demonstrated a significant average weight reduction of 11.15 kg (-
11.33% of total body weight) (p < 0.001) after 8 weeks of treatment (Table 1a). This reduction in
weight was accompanied by a loss of visceral fat, as measured by waist circumference and lipid
profiles [6]. The same trend was observed with overweight participants (Tables 2, 3, 4, 5).
The present study clearly demonstrates that administration of IGOB131 and Dyglomera™
can be used to prevent and manage weight increase, specifically targeting to limit the progression
to obesity and the myriad of its complications. The antioxidant properties of both extracts have
been intensively documented, and are suggested to be involved with curative activity [7].
However, there are only a few and controversial studies on oxidative stress in overweight
subjects compared to obesity studies [8]. For example, one study demonstrated that oxidative
stress increases with increasing BMI and age, as a sequel to an impaired antioxidant status, in
addition to an increase of peroxides and uric acid and a disadvantaged lipid profile in overweight
subjects. In contrast, another study [9] demonstrated that oxidative stress is not involved in the
overweight status. However, it is established that lipid peroxidation is associated with several
indices of adiposity and a low systemic antioxidant defense (i.e. antioxidant enzymes, tissue
dietary antioxidants, glutathione [10], and leading to oxidative stress. In fact, in stress conditions
ROS levels increase; because of their high reactivity, they are involved in cell damage, necrosis,
and apoptosis, via oxidation of lipids, proteins, and DNA, in addition to provoking an endothelial
dysfunction, infiltration, and activation of inflammatory cells [11]. The anti-oxidant property of
the IGOB131 used in this study can be attributed to the presence of ellagic acid (EA). This
polyphenolic compound has been shown to be antiproliferative and anti-inflammatory [12, 13].
Additionally, its efficacy in the management of obesity and metabolic syndrome has previously
been reported [6].
The present study has also proven the capacity of these extracts to reduce body fat (Table
1c), waist and hip circumferences (Tables 1d and 1e respectively), total cholesterol (Table 2),
triglyceride (Table 3), and LDL cholesterol levels (Table 4) in overweight participants. The
observed reduction may be due to the presence of EA in IGOB131. In fact, lipid accumulation
both in adipose tissue and liver are associated with increasing weight; progression to an
overweight condition [13] and changes in weight are partially due to the metabolic reactions and
Functional Foods in Health and Disease 2015; 5(6):200-208 Page 206 of 208
differentiation occurring in the adipose tissue. This can explain hypertrophy and hyperplastic
expansion of adipocytes associated with being overweight and obese. Furthermore, EA has a
lipid-lowering dietary compound; its inhibitory effects on adipogenesis seem to be associated, at
least partly, with epigenetic modification. EA decreases hepatic lipid accumulation by targeting
multiple mechanisms including FFA synthesis, TG sterification and FFA oxidation. In a recent
study [12], there was evidence that EA plays separate, differing roles in manipulating excess
lipid in adipocytes and hepatocytes, resulting in a synergistic attenuation the progression from
overweight state to obesity and hepatic steatosis. EA also exerted the distinctive lipid-lowering
properties to decrease biosynthesis of FA in both adipocytes and hepatocytes, but augmented FA
oxidation only in hepatocytes. The presence of EA in extracts has also been shown to be
effective in reducing atherosclerotic lesions and increasing cholesterol efflux in macrophages.
Additionally, constituents of IGOB131 and Dyglomera including EA, may act via modulation of
the expression of PPAR- gamma required for maintenance of the differentiated state of
adipocytes, which has been reported to be involved in lipid accumulation and decreased
expression of adipocyte markers. Several other transcription factors are likely to play an
important role in the molecular control of adipogenesis like C/EBPs [14]. The presence of
albumin in IGOB131 extracts may also contribute to the activity observed, although the function
is not well understood. Albumin has been demonstrated to bind reversibly to many endogenous
molecules (e.g., fatty acids), as well as pharmacologic agents [15]. It is speculated that this
combination to other constituents can play a much more important role in buffering against
sudden changes in absorption, thereby providing more consistent blood levels, similar to like
detemir, an insulin preparation [16]. Albumin may also contribute to prolonged duration of
action caused by some of the active compounds in our extracts. Other studies proved that the
addition of molecules like albumin, a soluble 66.5 kD monomeric, leads to significant
improvement in the solubility of the poorly soluble compounds [17. 18]. Another explanation for
the role of albumin in weight reduction and lipid profile can be described from its presence in
Whey protein. In fact, the presence of albumin in whey, a dietary protein which stimulates
energy expenditure, has a greater thermogenic effect in the postprandial period compared to
carbohydrates and fats, and additionally decreases energy intake through mechanisms that
influence appetite. Whey amino acids on insulin secretion, incretin hormones released from the
gut, also seem to be involved, in particular gastric inhibitory peptide (GIP) and glucagon-like
peptide 1 (GLP-1). Furthermore, the presence of albumin in our extracts could influence
absorption process at the intestinal level, considering that the postprandial rate of protein
synthesis also depends on the speed of protein absorption and that fast absorbing protein has an
anabolic effect [19].
Abbreviations Used: GLP1, glucagon-like peptide; GIP, gastric inhibitory peptide; BMI, body
mass index; FFA, free fatty acids; TG, triglyceride; PPAR, peroxisome proliferator-activated
receptors; EA; ellagic acid; ROS, reactive oxygen species; LDL, low density lipoprotein; HDL,
high density lipoprotein ; DG, Dyglomera™, extract of Dichrostachys glomerata; IGOB131,
extract of Irvingia gabonensis.
Competing Interests: The authors have no financial interests or conflicts of interest.
Functional Foods in Health and Disease 2015; 5(6):200-208 Page 207 of 208
Authors’ Contributions: All authors contributed to this study.
Acknowledgements and Funding: The authors would like to thank the School of Health
Sciences, Universiti Sains, Malaysia for financial support for Dieudonne Kuate and also for an
ICCBS-TWAS Sandwich Postgraduate Fellowship for Ghislain Paka.
REFERENCES:
1. Shirin H-R, Jouyandeh Z, Abdollahi M. A systematic review of anti-obesity medicinal
plants - an update. J Diabetes Metab Disord 2013; 12: 28 doi: 10.1186/2251-6581-12-
28.
2. Bray GA. Medical consequences of obesity. J Clin Endocrinol Metab. 2004; 89(6):
2583–2589.
3. Taghizadeh M, Memarzadeh MR, Asemi Z, Esmaillzadeh A. Effect of the cumin
cyminum L. Intake on Weight Loss, Metabolic Profiles and Biomarkers of Oxidative
Stress in Overweight Subjects: A Randomized Double-Blind Placebo-Controlled
Clinical Trial. Ann Nutr Metab. 2015; 3; 66(2-3):117-124.
4. Ngondi JL, Etoundi BC, Nyangono CB, Mbofung CM, Oben JE. IGOB131, a novel
seed extract of the West African plant Irvingia gabonensis, significantly reduces body
weight and improves metabolic parameters in overweight humans in a randomized
double-blind placebo controlled investigation. Lipids Health Dis. 2009; 2;8:7. doi:
10.1186/1476-511X-8-7.
5. Oben J, Ngondi J, Blum K. Inhibition of Irvingia gabonensis seed extract (OB131) on
adipogenesis as mediated via down regulation of the PPARgamma and leptin genes
and up-regulation of the adiponectin gene. Lipids Health Dis. 2008; 7: 44
doi:10:1186/1476-511X-7-44
6. Kuate D, Etoundi BC, Ngondi JL, Manan WA, Muda BW, Oben JE. Anti-
inflammatory, anthropometric and lipomodulatory effects Dyglomera® (aqueous
extract of Dichrostachys glomerata) in obese patients with metabolic syndrome.
Functional Foods in Health and Disease 2013; 3(11): 416-427
7. Kuate D, Etoundi BCO, Soukontoua YB, Ngondi JL, Oben JE. Antioxidant
characteristics of Dichrostachys glomerata spice extracts. CyTA – J. Food 2010; 8:
23–37.
8. Wonisch W, Falk A, Sundl I, Winklhofer-Roob BM, Lindschinger M. Oxidative stress
increases continuously with BMI and age with unfavorable profiles in males. Aging
Male. 2012; 15(3): 159-65. doi: 10.3109/13685538.2012.669436.
9. Venturini D, Simão AN, Scripes NA, Bahls LD, Melo PA, Belinetti FM, Lozovoy
MA, Dichi I. Evaluation of oxidative stress in overweight subjects with or without
metabolic syndrome. Obesity (Silver Spring). 2012; 20(12): 2361-6. doi:
10.1038/oby.2012.130. Epub 2012 May 17.
10. Vincent HK, Innes KE, Vincent KR. Oxidative stress and potential interventions to
reduce oxidative stress in overweight and obesity. Diabetes Obes Metab. 2007; 9(6):
813-839.
Functional Foods in Health and Disease 2015; 5(6):200-208 Page 208 of 208
11. Marchi ED, Baldassari F, Bononi A., Wieckowski MR, Pinton P. Oxidative Stress in
Cardiovascular Diseases and Obesity: Role of p66Shc and Protein Kinase C. Oxidative
Medicine and Cellular Longevity 2013; 11. , http://dx.doi.org/10.1155/2013/564961
12. Meshail O, Kang I, Kim DM, Gourineni V, Shay N, Gu L, Chung S. Ellagic acid
modulates lipid accumulation in primary human adipocytes and human hepatoma
Huh7 cells via discrete mechanisms. J Nutr Biochem. 2015; 26, I 1: 82–90.
13. Moreno-Navarrete JM, Fernández-Real JM. Adipocyte differentiation. Adipose Tissue
Biology, Symonds ME. (Ed), 2012; VI, 414 P, http://www.springer.com/978-1-4614-
0964-9.
14. Tamori Y, Masugi J, Nishino N, Kasuga M. Role of peroxisome proliferator-activated
receptor- g in maintenance of the characteristics of mature 3T3-L1 adipocytes.
Diabetes 2002; 51: 2045–2055
15. Chaykin L. Insulin Detemir and Its Unique Mechanism of Action. The Internet Journal
of Endocrinology. 2006; 4 :1.
16. Shimmura S, Ueno R, Matsumoto Y, Goto YE, Higuchi A, Shimazaki JK. Albumin as
a tear supplement in the treatment of severe dry eye. Br J Ophthalmol. 2003; 87(10):
1279–1283.
17. Shah D, Paruchury S, Matta M, Chowan G, Subramanian M, Saxena A, Soars MG,
Herbst J, Haskell R, Marathe P, Mandlekar SA. systematic evaluation of solubility
enhancing excipients to enable the generation of permeability data for poorly soluble
compounds in caco-2 model. Drug Metab Lett. 2014; 8(2): 109-118.
18. Majcher A, Lewandrowska A, Herold F, Stefanowicz J, Słowiński T, Mazurek AP,
Wieczorek SA, Hołyst R. A method for rapid screening of interactions of
pharmacologically active compounds with albumin. Anal Chim Acta. 2015; Jan
15;855:51-9. doi: 10.1016/j.aca.2014.12.008. Epub 2014 Dec 10.
19. Jakubowicz D, Oren F. Biochemical and metabolic mechanisms by which dietary
whey protein may combat obesity and Type 2 diabetes. J Nutr Biochem. 2013; 24: 1–
5.