Attenuation Of Obesity Research Articles

Lifestyle Modification Exerts Protection Against Obesity‐Induced Neurodegeneration Via CD147‐Related Mechanism

AbstractBackgroundCD147, also known as extracellular matrix metalloproteinase inducer, is a key mediator of inflammatory and immune responses in various kinds of neurodegenerative disease (1). However, the role of CD147 in obesity‐induced neurodegeneration has not been previously investigated. Therefore, this study aims to investigate the alteration of CD147 expression in the hippocampus of obese rats, both with and without lifestyle modification.MethodSeven‐week‐old male Wistar rats were divided into 4 groups (n = 5 per group), including 1) rats fed with a normal diet for 28 weeks [ND], 2) rats fed with a high‐fat diet (HFD) for 28 weeks [HFD], 3) rats fed with a HFD for 12 weeks followed by 40% caloric restriction for an additional 16 weeks [HFD‐CR], or 4) rats fed with a HFD for 12 weeks followed by exercise plus HFD for an additional 16 weeks [HFD‐EX]. At the end of week 28, cognitive function was determined by a novel object location test. The rats were then euthanized on the following day for molecular studies in the hippocampus.ResultWe found that hippocampal CD147 level exerted a strongly negative correlation with the level of cognitive function (Figure A). In addition, CD147 expression and its downstream consequences – p‐NFκB, MMP‐9, and TNF‐α – were upregulated in HFD‐fed rats (Figure B‐E). The HFD‐fed rats also exhibited an increase in activated microglia (CD68), along with decreased blood‐brain barrier protein (claudin‐5), dendritic spine density, and cognitive performance (Figure F‐I). Strikingly, both caloric restriction and exercise effectively reduced the expression of CD147 and its downstream consequences, as well as restored CD68, claudin‐5, dendritic spine density, and cognitive function in HFD‐fed rats (Figure B‐I).ConclusionOur findings suggested that CD147 is one of the detrimental mediators in obesity‐induced neurodegeneration (Figure J). Interestingly, an attenuation of obesity by lifestyle modification exerts protection against cognitive impairment via CD147‐related mechanisms (Figure J). Therefore, an inhibition of CD147 is considered as a therapeutic target to prevent cognitive impairment in obese individuals. Reference 1. Kaushik DK, Hahn JN, Yong VW. EMMPRIN, an upstream regulator of MMPs, in CNS biology. Matrix Biol. 2015;44‐46:138‐46.

Nutritional quality and health benefits of roselle calyces

Abstract Roselle calyces (Hibiscus sabdariffa L.) were evaluated through a critical study of existing research works on health benefits, mineral compositions, bioactive compositions, mechanisms, and possible research gaps. The use of roselle calyces as an alternative to synthetic food dyes, addressing growing global challenges of overweight, obesity, and cardiovascular diseases, was evaluated and encouraged. Studies indicate the attenuation of obesity by chlorogenic acid (the predominant phenolic compound in roselle calyx) via mechanisms associated with the UCP-1 and PGC-1α pathways, resulting in reduced blood lipid levels, reduced fat accumulation in the liver, and increased thermogenesis through fat metabolism. Minimum inhibitory concentration (MIC) of known bacteria and fungi, such as Listeria monocytogenes, Escherichia coli, Bacillus cereus, Salmonella typhimurium, Candida tropicalis, and Candida krusei, were studied. More research, however, needs to be conducted on organic acids present in roselle calyces to look into their possible applications and maximize their possible benefits.

Ferulic acid improves intestinal barrier function through altering gut microbiota composition in high-fat diet-induced mice.

A high-fat diet (HFD) induces gut microbiota (GM) disorders, leading to intestinal barrier dysfunction and inflammation. Ferulic acid (FA) has shown anti-obesity effects, e.g., reducing body weight and food intake. However, the mechanism linking the anti-obesity effects of FA and GM modulation remains obscure. The present study aimed to clarify the mechanism underlying the anti-obesity effects of FA and modulation of the GM. C57BL/6J mice were fed by a low-fat diet (LFD) and HFD with or without FA at a dose of 100mg/kg of body weight by oral gavage for 12weeks. Using high-throughput sequencing, gas chromatography, real-time fluorescence quantitative PCR and immunohistochemical staining, the attenuation of obesity by FA were assessed via intestinal barrier integrity, inflammation, and the GM. FA reduced weight gain, improved HFD-induced GM imbalance, significantly enhanced intestinal short-chain fatty acid (SCFA)-producing bacteria (e.g., Olsenella, Eisenbergiella, Dubosiella, Clostridiales_unclassified, and Faecalibaculum) along with SCFA accumulation and its receptors' expression, decreased endotoxin-producing bacteria or obesity-related bacterial genera, and serum endotoxin (lipopolysaccharides), and inhibited the colonic TLR4/NF-κB pathway. Thus, FA can mitigate colonic barrier dysfunction and intestinal inflammation, induce the production of SCFAs and inhibit endotoxins by modulating the GM. These results indicate that enhancement of intestinal barrier by altering the GM may be an anti-obesity target of FA and that FA can be used as a functional compound with great developmental values.

Protective Effects of Polyphenol Enriched Complex Plants Extract on Metabolic Dysfunctions Associated with Obesity and Related Nonalcoholic Fatty Liver Diseases in High Fat Diet-Induced C57BL/6 Mice.

Background: Currently, obesity is a global health challenge due to its increasing prevalence and associated health risk. It is associated with various metabolic diseases, including diabetes, hypertension, cardiovascular disease, stroke, certain forms of cancer, and non-alcoholic liver diseases (NAFLD). Objective: The aim of this study to evaluate the effects of polyphenol enriched herbal complex (Rubus crataegifolius/ellagic acid, Crataegus pinnatifida Bunge/vitexin, chlorogenic acid, Cinnamomum cassiaa/cinnamic acid) on obesity and obesity induced NAFLD in the high-fat diet (HFD)-induced obese mouse model. Methods: Obesity was induced in male C57BL/6 mice using HFD. After 8 weeks, the mice were treated with HFD+ plants extract for 8 weeks. Body weight, food intake weekly, and blood sugar level were measured. After sacrifice, changes in the treated group’s liver weight, fat weight, serum biochemical parameters, hormone levels, and enzyme levels were measured. For histological analysis, tissues were stained with hematoxylin-eosin (H&E) and Oil Red-O. Results: Our results showed that the herbal complex ameliorated body weight and liver weight gain, and decreased total body fat in HFD-fed animals. Post prandial blood glucose (PBG) and fasting blood glucose (FBG) were lower in the herbal complex-treated group than in the HFD control group. Additionally, herbal formulation treatment significantly increased HDL levels in serum and decreased TC, TG, AST, ALT, deposition of fat droplets in the liver, and intima media thickness (IMT) in the aorta. Herbal complex increased serum adiponectin and decreased serum leptin. Herbal complex also increased carnitine palmityl transferase (CPT) activity and significantly decreased enzyme activity of beta-hydroxy beta methyl glutamyl-CoA (HMG-CoA) reductase, and fatty acid synthase (FAS). Conclusions: The results of this study demonstrated that the herbal complex is an effective herbal formulation in the attenuation of obesity and obesity-induced metabolic dysfunction including NAFLD in HFD-induced mouse model.

A proprotein convertase subtilisin/kexin type 9 inhibitor provides comparable efficacy with lower detriment than statins on mitochondria of oxidative muscle of obese estrogen-deprived rats.

The aim of the study was to compare the effects of atorvastatin, a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i), and 17β-estradiol on oxidative muscle mitochondria in a model of menopause with obesity. Female Wistar rats consumed either a standard diet (n = 12) or a high-fat/calorie diet (HFCD: n = 60). At week 13, standard diet-fed rats underwent a sham operation, whereas HFCD-fed rats underwent either a sham operation (n = 12) or an ovariectomy (n = 48). At week 19, all sham-operated rats received vehicle, and ovariectomized HFCD-fed rats received either vehicle, 40 mg/kg/d of atorvastatin, 4 mg/kg/d of PCSK9i (SBC-115076), or 50 μg/kg/d of 17β-estradiol for 3 weeks (n = 12/group). Metabolic parameters and soleus muscle physiology were investigated at the end of week 21. Sham-operated and ovariectomized HFCD-fed rats developed obesity, hyperlipidemia, and insulin resistance, also showing increased oxidative phosphorylation (OXPHOS) proteins, ratio of p-Drp1-to-total Drp1 protein, malondialdehyde level, mitochondrial reactive oxygen species, and mitochondrial membrane depolarization in soleus muscle. All drugs equally decreased insulin resistance, OXPHOS proteins, ratio of p-Drp1-to-total Drp1 protein, and malondialdehyde level in soleus muscle. Only atorvastatin and PCSK9i attenuated hypertriglyceridemia, whereas 17β-estradiol had greater efficacy in preventing weight gain than the other two drugs. In addition, 17β-estradiol decreased mitochondrial reactive oxygen species and mitochondrial membrane depolarization. Atorvastatin increased ratio of cleaved caspase 3,8-to-procaspase 3,8, and cytochrome C. 17β-Estradiol exhibits the greatest efficacy on the attenuation of obesity with the least harmful effect on skeletal muscle in a model of menopause with obesity, yet its effect on the treatment of hyperlipidemia is inferior to those of standard lipid-lowering agents.

Fuzhuan Brick Tea Attenuates High-Fat Diet-Induced Obesity and Associated Metabolic Disorders by Shaping Gut Microbiota.

An increasing amount of evidence suggests that the metabolic improvement of high-fat diet (HFD)-induced obese mice by Fuzhuan brick tea (FBT) is associated with gut microbiota. However, the causalities between FBT and gut microbiota have not yet been elucidated and the underlying mechanisms of action remain unclear. To impart direct evidence for the essential role of gut microbiota in the attenuation of obesity by FBT, the effects of FBT on healthy mice and microbiota-depleted mice that were treated with antibiotics were compared in an HFD-induced obesity mouse model. The results showed that FBT dramatically ameliorated obesity, serum lipid parameters, blood glucose homeostasis, hepatic steatosis, adipocyte hypertrophy, and tissue inflammation. However, the microbiota-depleted mice with single bacterium (Escherichia-Shigella) after antibiotic treatment were resistant to FBT-induced antiobesity and metabolic improvement. The beneficial effects of FBT resulted from its shift on gut microbiota composition and structure in mice. HFD-induced increase in the phyla Firmicutes/Bacteroidetes (F/B) ratio was remarkably restored by FBT. Furthermore, FBT-induced increase in abundances of beneficial bacteria Clostridiaceae, Bacteroidales, and Lachnospiraceae and decreases in harmful Ruminococcaceae, Peptococcaceae, Peptostreptococcaceae, and Erysipelotrichaceae were causal antecedents for FBT to reduce obesity and improve metabolic disorders.

Morus alba L. Diminishes visceral adiposity, insulin resistance, behavioral alterations via regulation of gene expression of leptin, resistin and adiponectin in rats fed a high-cholesterol diet

Ethanolic extract of leaves of Morus alba L. (M. alba), known as white mulberry, was orally administered (100 mg/kg b.wt) for 8 weeks to female Wistar rats that were fed a high-cholesterol diet (HCD), to investigate the potential of M. alba leaves in attenuation of obesity, dyslipidemia, insulin resistance, and deficits in mood, cognitive as well as motor activity that are linked to the adipokines secretions of visceral adipose tissue. Results showed that M. alba diminished body weight gain, hypercholesterolemia, hypertriglyceridemia, atherogenic (AI) & coronary artery indices (CRI), and ameliorated glucose level and insulin resistance index in rats on HCD, compared with untreated HCD rats. Moreover, M. alba administration significantly decreased serum leptin and resistin contents as well as their mRNA expression in visceral adipose tissue, but significantly increased serum adiponectin level, and its mRNA expression in visceral adipose tissue in rats fed on HCD, compared to those in untreated HCD group. Regarding behavioral alterations, M. alba attenuated motor deficit, declined memory, depression and anxiety-like behavior, as well in rats on HCD, compared to that noticed in untreated HCD rats. The current data showed that serum leptin and resistin showed a positive correlation with and body weight gain, triglycerides (TG), AI as well as CRI, but showed a negative correlation with exploration, declined memory, depression- and anxiety-like behavior. Conversely, serum adiponectin showed a negative correlation with and body weight gain, TG, AI as well as CRI, but showed a positive correlation with locomotor activity, exploration, declined memory, and depression- and anxiety-like behavior. In conclusion, M. alba leaves supplementation could attenuate adiposity, insulin resistance behavioral deficits via down-regulation of regulation of gene expression of leptin, resistin, but up-regulation of adiponectin gene expression in the visceral adipose tissue of rats fed a high-cholesterol diet.

Attenuation of obesity and insulin resistance by fish oil supplementation is associated with improved skeletal muscle mitochondrial function in mice fed a high-fat diet

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been reported to improve insulin sensitivity and glucose homeostasis in animal models of insulin resistance, but the involved mechanisms still remain unresolved. In this study, we evaluated the effects of fish oil (FO), a source of n-3 PUFAs, on obesity, insulin resistance and muscle mitochondrial function in mice fed a high-fat diet (HFD). C57Bl/6 male mice, 8 weeks old, were divided into four groups: control diet (C), high-fat diet (H), C+FO (CFO) and H+FO (HFO). FO was administered by oral gavage (2 g/kg b.w.), three times a week, starting 4 weeks before diet administration until the end of the experimental protocol. HFD-induced obesity and insulin resistance associated with impaired skeletal muscle mitochondrial function, as indicated by decreased oxygen consumption, tricarboxylic acid cycle intermediate (TCAi) contents (citrate, α-ketoglutarate, malate and oxaloacetate), oxidative phosphorylation protein content and mitochondrial biogenesis. These effects were associated with elevated reactive oxygen species production, decreased PGC1-a transcription and reduced Akt phosphorylation. The changes induced by the HFD were partially attenuated by FO, which decreased obesity and insulin resistance and increased mitochondrial function. In the H group, FO supplementation also improved oxygen consumption; increased TCAi content, and Akt and AMPK phosphorylation; and up-regulated mRNA expression of Gpat1, Pepck, catalase and mitochondrial proteins (Pgc1α, Pparα, Cpt1 and Ucp3). These results suggest that dietary FO attenuates the deleterious effects of the HFD (obesity and insulin resistance) by improving skeletal muscle mitochondrial function.

Breastfeeding Is Associated With Reduced Obesity in Hispanic 2- to 5-Year-Olds Served by WIC

ObjectiveTo examine the relationship between breastfeeding (BF) and odds of childhood obesity in a large, primarily Hispanic Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) population. SettingA large urban WIC program in California. ParticipantsInfants enrolled in WIC born between 2004 and 2007 and observed to age 5 years (N = 39,801; 88.6% Hispanic). InterventionLevel of BF: fully BF, fully formula feeding, or combination feeding. Main Outcome MeasureObesity at age 2–5 years, measured by body mass index (BMI) ≥ 95th percentile. AnalysisLogistic regression analyses to evaluate the association between initiation, duration, and exclusivity of BF and odds of obesity at age 2–5 years, controlling for ethnicity, preferred language, family size, poverty level, and maternal BMI. ResultsInfants exclusively formula fed at birth were significantly more likely than fully breastfed infants to be obese at age 2–5 years (χ2 [2, N = 39,801] = 123.31; P < .001). For every additional month of any BF, obesity risk at age 2–5 years decreased by 1%. Every additional month of full BF conferred a 3% decrease in obesity risk. Ethnicity, preferred language, family size, poverty level, and maternal BMI were also significantly related to obesity risk. Conclusions and ImplicationsBreastfeeding may have a role in the attenuation of obesity in early childhood among Hispanic children. The BF promotion and support offered at WIC may have a significant role in reducing rates of early childhood obesity.

Daesiho-Tang Is an Effective Herbal Formulation in Attenuation of Obesity in Mice through Alteration of Gene Expression and Modulation of Intestinal Microbiota.

BackgroundObesity has become a major global health challenge due to its increasing prevalence, and the associated health risk. It is the main cause of various metabolic diseases including diabetes, hypertension, cardiovascular disease, stroke and certain forms of cancer.Methods and ResultsIn the present study we evaluated the anti-obesity property of Daesiho-tang (DSHT), an herbal medicine, using high fat diet (HFD)-induced obese mice as a model. Our results showed that DSHT ameliorated body weight gain, decreased total body fat, regulated expression of leptin and adiponectin genes of adipose tissue and exerted an anti-diabetic effect by attenuating fasting glucose level and serum insulin level in HFD-fed animals. In addition, DSHT-treatment significantly reduced total cholesterol (TC), triglycerides (TG) and increased high density lipoprotein-cholesterol (HDL), glutamic pyruvic transaminase (GPT) and glutamic oxaloacetic transaminase (GOT) levels in serum and reduced deposition of fat droplets in liver. DSHT treatment resulted in significantly increased relative abundance of bacteria including Bacteroidetes, Bacteroidetes/Firmicutes ratio, Akkermansia Bifidobacterium., Lactobacillus, and decreased the level of Firmicutes. Using RT2 profiler PCR array, 39 (46%) genes were found to be differentially expressed in HFD-fed mice compared to normal control. However, normal gene expressions were restored in 36 (92%) genes of HFD-fed mice, when co-exposed to DSHT.Conclusion/Major FindingsThe results of this study demonstrated that DSHT is an effective herbal formulation in attenuation of obesity in HFD-fed mice through alteration of gene expressions and modulation of intestinal microbiota.

Attenuation of obesity by early-life food restriction in genetically hyperphagic male OLETF rats: Peripheral mechanisms

The alarming increase in childhood, adolescent and adult obesity has exposed the need for understanding early factors affecting obesity and for treatments that may help prevent or moderate its development. In the present study, we used the OLETF rat model of early-onset hyperphagia induced obesity, which become obese as a result of the absence of CCK 1 receptors, to examine the influence of partial food restriction on peripheral adiposity-related parameters during and after chronic and early short-term food restriction. Pair feeding (to the amount of food eaten by control, LETO rats) took place from weaning until postnatal day (PND) 45 ( early) or from weaning until PND90 ( chronic). We examined fat pad weight (brown, retroperitoneal, inguinal and epididymal); inguinal adipocyte size and number; and plasma leptin, oxytocin and creatinine levels. We also examined body weight, feeding efficiency and spontaneous intake after release from food-restriction. The results showed that chronic food restriction produced significant reductions in adiposity parameters, hormones and body weight, while early food restriction successfully reduced long-term body weight, intake and adiposity, without affecting plasma measurements. Early (and chronic) dieting produced promising long-term effects that may imply the reorganization of both peripheral and central mechanisms that determine energy balance and further support the theory suggesting that early interventions may effectively moderate obesity, even in the presence of a genetic tendency.

Attenuation of obesity, insulin resistance, and inflammation in TLR4 deficient 10ScN mice in response to a diet high in saturated fat

Attenuation of obesity, insulin resistance, and inflammation in TLR4 deficient 10ScN mice in response to a diet high in saturated fat

Improvement of diabetes, obesity and hypertension in type 2 diabetic KKA y mice by bis(allixinato)oxovanadium(IV) complex

Previously, we found that bis(allixinato)oxovanadium(IV) (VO(alx) 2) exhibits a potent hypoglycemic activity in type 1-like diabetic mice. Since the enhancement of insulin sensitivity is involved in one of the mechanisms by which vanadium exerts its anti-diabetic effects, VO(alx) 2 was further tested in type 2 diabetes with low insulin sensitivity. The effect of oral administration of VO(alx) 2 was examined in obesity-linked type 2 diabetic KKA y mice. Treatment of VO(alx) 2 for 4 weeks normalized hyperglycemia, glucose intolerance, hyperinsulinemia, hypercholesterolemia and hypertension in KKA y mice; however, it had no effect on hypoadiponectinemia. VO(alx) 2 also improved hyperleptinemia, following attenuation of obesity in KKA y mice. This is the first example in which a vanadium compound improved leptin resistance in type 2 diabetes by oral administration. On the basis of these results, VO(alx) 2 is proposed to enhance not only insulin sensitivity but also leptin sensitivity, which in turn improves diabetes, obesity and hypertension in an obesity-linked type 2 diabetic animal.