Reduction In Adipose Tissue Weight Research Articles

Effects of astaxanthin in animal models of obesity-associated diseases: A systematic review and meta-analysis

Background and aimObesity is a major risk factor for several diseases, including metabolic syndrome (MetS), non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D). The use of natural products, such as astaxanthin (ASX), a potent antioxidant compound produced by the freshwater green microalga Haematococcus pluvialis, has gained particular interest to reduce oxidative stress and inflammation, and to improve redox status, often associated with obesity. A systematic review and meta-analysis was performed to comprehensively examine the effects of ASX in animal models of diet induced obesity-associated diseases in order to inform the design of future human clinical studies for ASX use as supplement or nutraceutical. MethodsCinahl, Cochraine, MEDLINE, Scopus and Web of Science were searched for English-language manuscripts published between January 2000 and April 2020 using the following key words: astaxanthin, obesity, non-alcoholic fatty liver disease, diabetes mellitus type 2, NAFLD and metabolic. ResultsSeventeen eligible articles, corresponding to 21 animal studies, were included in the final quantitative analysis. ASX, at different concentrations and administered for different length of time, induced a significant reduction in adipose tissue weight (P = 0.05) and systolic blood pressure (P < 0.0001) in control animals. In animal models of T2D, ASX significantly reduced serum glucose levels (P = 0.04); whereas it improved several disease biomarkers in the blood (e.g. cholesterol, triglycerides, ALT and AST, P < 0.10), and reduced liver (P = 0.0002) and body weight (P = 0.11), in animal models of NAFLD. ConclusionsSupplementation of ASX in the diet has positive effects on symptoms associated with obesity related diseases in animals, by having lipid-lowering, hypo-insulin and hypoglycaemic capacity, protecting organs from oxidative stress and mitigating the immune system, as suggested in this review.

Antiobesity Effect of Exopolysaccharides Isolated from Kefir Grains.

Physiological properties of water-soluble exopolysaccharides (EPS) and residues after EPS removal (Res) from the probiotic kefir were determined in high-fat (HF) diet-fed C57BL/6J mice. EPS solutions showed rheological properties and lower viscosity compared to those of β-glucan (BG). EPS significantly suppressed the adipogenesis of 3T3-L1 preadipocytes in a dose-dependent manner. Mice were fed HF diets containing 5% EPS, 5% BG, 8% Res, or 5% microcrystalline cellulose (control) for 4 weeks. Compared with the control, EPS supplementation significantly reduced HF diet-induced body weight gain, adipose tissue weight, and plasma very-low-density lipoprotein cholesterol concentration (P < 0.05). Res and BG significantly reduced body weight gain; however, reduction in adipose tissue weight was not statistically significant, suggesting that the antiobesity effect of EPS occurs due to viscosity and an additional factor. EPS supplementation significantly enhanced abundance of Akkermansia spp. in feces. These data indicate that EPS shows significant antiobesity effects possibly via intestinal microbiota alterations.

Adipose tissue (P)RR regulates insulin sensitivity, fat mass and body weight

ObjectiveWe previously demonstrated that the handle-region peptide, a prorenin/renin receptor [(P)RR] blocker, reduces body weight and fat mass and may improve insulin sensitivity in high-fat fed mice. We hypothesized that knocking out the adipose tissue (P)RR gene would prevent weight gain and insulin resistance. MethodsAn adipose tissue-specific (P)RR knockout (KO) mouse was created by Cre-loxP technology using AP2-Cre recombinase mice. Because the (P)RR gene is located on the X chromosome, hemizygous males were complete KO and had a more pronounced phenotype on a normal diet (ND) diet compared to heterozygous KO females. Therefore, we challenged the female mice with a high-fat diet (HFD) to uncover certain phenotypes. Mice were maintained on either diet for 9 weeks. ResultsKO mice had lower body weights compared to wild-types (WT). Only hemizygous male KO mice presented with lower total fat mass, higher total lean mass as well as smaller adipocytes compared to WT mice. Although food intake was similar between genotypes, locomotor activity during the active period was increased in both male and female KO mice. Interestingly, only male KO mice had increased O2 consumption and CO2 production during the entire 24-hour period, suggesting an increased basal metabolic rate. Although glycemia during a glucose tolerance test was similar, KO males as well as HFD-fed females had lower plasma insulin and C-peptide levels compared to WT mice, suggesting improved insulin sensitivity. Remarkably, all KO animals exhibited higher circulating adiponectin levels, suggesting that this phenotype can occur even in the absence of a significant reduction in adipose tissue weight, as observed in females and, thus, may be a specific effect related to the (P)RR. Conclusions(P)RR may be an important therapeutic target for the treatment of obesity and its associated complications such as type 2 diabetes.

Small Molecular Allosteric Activator of the Sarco/Endoplasmic Reticulum Ca2+-ATPase (SERCA) Attenuates Diabetes and Metabolic Disorders

Dysregulation of endoplasmic reticulum (ER) Ca(2+) homeostasis triggers ER stress leading to the development of insulin resistance in obesity and diabetes. Impaired function of the sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) has emerged as a major contributor to ER stress. We pharmacologically activated SERCA2b in a genetic model of insulin resistance and type 2 diabetes (ob/ob mice) with a novel allosteric activator, CDN1163, which markedly lowered fasting blood glucose, improved glucose tolerance, and ameliorated hepatosteatosis but did not alter glucose levels or body weight in lean controls. Importantly, CDN1163-treated ob/ob mice maintained euglycemia comparable with that of lean mice for >6 weeks after cessation of CDN1163 administration. CDN1163-treated ob/ob mice showed a significant reduction in adipose tissue weight with no change in lean mass, assessed by magnetic resonance imaging. They also showed an increase in energy expenditure using indirect calorimetry, which was accompanied by increased expression of uncoupling protein 1 (UCP1) and UCP3 in brown adipose tissue. CDN1163 treatment significantly reduced the hepatic expression of genes involved in gluconeogenesis and lipogenesis, attenuated ER stress response and ER stress-induced apoptosis, and improved mitochondrial biogenesis, possibly through SERCA2-mediated activation of AMP-activated protein kinase pathway. The findings suggest that SERCA2b activation may hold promise as an effective therapy for type-2 diabetes and metabolic dysfunction.

Angiotensin II receptor blocker ameliorates stress-induced adipose tissue inflammation and insulin resistance.

A strong causal link exists between psychological stress and insulin resistance as well with hypertension. Meanwhile, stress-related responses play critical roles in glucose metabolism in hypertensive patients. As clinical trials suggest that angiotensin-receptor blocker delays the onset of diabetes in hypertensive patients, we investigated the effects of irbesartan on stress-induced adipose tissue inflammation and insulin resistance. C57BL/6J mice were subjected to 2-week intermittent restraint stress and orally treated with vehicle, 3 and 10 mg/kg/day irbesartan. The plasma concentrations of lipid and proinflammatory cytokines [Monocyte Chemoattractant Protein-1 (MCP-1), tumor necrosis factor-α, and interleukin-6] were assessed with enzyme-linked immunosorbent assay. Monocyte/macrophage accumulation in inguinal white adipose tissue (WAT) was observed with CD11b-positive cell counts and mRNA expressions of CD68 and F4/80 using immunohistochemistry and RT-PCR methods respectively. The mRNA levels of angiotensinogen, proinflammatory cytokines shown above, and adiponectin in WAT were also assessed with RT-PCR method. Glucose metabolism was assessed by glucose tolerance tests (GTTs) and insulin tolerance tests, and mRNA expression of insulin receptor substrate-1 (IRS-1) and glucose transporter 4 (GLUT4) in WAT. Restraint stress increased monocyte accumulation, plasma free fatty acids, expression of angiotensinogen and proinflammatory cytokines including MCP-1, and reduced adiponectin. Irbesartan reduced stress-induced monocyte accumulation in WAT in a dose dependent manner. Irbesartan treatment also suppressed induction of adipose angiotensinogen and proinflammatory cytokines in WAT and blood, and reversed changes in adiponectin expression. Notably, irbesartan suppressed stress-induced reduction in adipose tissue weight and free fatty acid release, and improved insulin tolerance with restoration of IRS-1 and GLUT4 mRNA expressions in WAT. The results indicate that irbesartan improves stress-induced adipose tissue inflammation and insulin resistance. Our results suggests that irbesartan treatment exerts additive benefits for glucose metabolism in hypertensive patients with mental stress.

A clinical and biological evaluation of a novel, noninvasive radiofrequency device for the long‐term reduction of adipose tissue

A novel, noninvasive technology, utilizing suction-coupled radiofrequency (RF) heating and ultra-short pulse duration, high-voltage electrical pulses was studied for its efficacy and safety on adipose tissue reduction. Twenty-one subjects underwent treatment of their abdominal fat once weekly for 6 weeks. Clinical outcomes including abdominal circumference, adipose tissue thickness (measured by ultrasound), adipose tissue weight, body weight, and clinical photographs were obtained at visits 1 and 3 months after last treatment. Adverse events were recorded. Three subjects, who were undergoing a future elective abdominoplasty, were treated with the same protocol, but on only one side of the abdomen before abdominoplasty. Biopsies from the RF-treated and untreated sides were harvested during abdominoplasty and cultured; measurements of adipocyte size and shape, rate of apoptosis, collagen production, and dermal thickness were determined. Significant clinical improvements (P < 0.05) were observed for the following clinical outcomes: reduction of abdominal circumference (113.4-110.7 cm), reduction of subcutaneous adipose tissue thickness (40.5-38.5 mm), and reduction in adipose tissue weight (32.2-30.7 kg) at 3-month follow-up visits. Overall patient weight also decreased, which was statistically significant at 1-month follow-up, but was not statistically significant at 3-month follow-up (73.9-73.3 kg, P = 0.609). Histologically, adipocytes were observed to have decreased size and withered shape, with increased levels of apoptosis; increased collagen synthesis, with compaction and reorganization of the dermis was also observed. Only minor, transient side effects were reported. This novel, noninvasive RF device was effective for improving subcutaneous fat, reducing abdominal circumference and reducing subcutaneous fat layer thickness. Histologically, these improvements appear to be partly related to increased adipocyte apoptosis.

Dietary β-conglycinin prevents fatty liver induced by a high-fat diet by a decrease in peroxisome proliferator-activated receptor γ2 protein

Diets high in sucrose/fructose or fat can result in hepatic steatosis (fatty liver). Mice fed a high-fat diet, especially that of saturated-fat-rich oil, develop fatty liver with an increase in peroxisome proliferator-activated receptor (PPAR) γ2 protein in liver. The fatty liver induced by a high-fat diet is improved by knockdown of liver PPARγ2. In this study, we investigated whether β-conglycinin (a major protein of soy protein) could reduce PPARγ2 protein and prevent high-fat-diet-induced fatty liver in ddY mice. Mice were fed a high-starch diet (70 energy% [en%] starch) plus 20% (wt/wt) sucrose in their drinking water or a high-safflower-oil diet (60 en%) or a high-butter diet (60 en%) for 11 weeks, by which fatty liver is developed. As a control, mice were fed a high-starch diet with drinking water. Either β-conglycinin or casein (control) was given as dietary protein. β-Conglycinin supplementation completely prevented fatty liver induced by each type of diet, along with a reduction in adipose tissue weight. β-Conglycinin decreased sterol regulatory element-binding protein (SREBP)-1c and carbohydrate response element-binding protein (ChREBP) messenger RNAs (mRNAs) in sucrose-supplemented mice, whereas it decreased PPARγ2 mRNA (and its target genes CD36 and FSP27), but did not decrease SREBP-1c and ChREBP mRNAs, in mice fed a high-fat diet. β-Conglycinin decreased PPARγ2 protein and liver triglyceride (TG) concentration in a dose-dependent manner in mice fed a high-butter diet; a significant decrease in liver TG concentration was observed at a concentration of 15 en%. In conclusion, β-conglycinin effectively prevents fatty liver induced by a high-fat diet through a decrease in liver PPARγ2 protein.

The Fasting-induced Adipose Factor/Angiopoietin-like Protein 4 Is Physically Associated with Lipoproteins and Governs Plasma Lipid Levels and Adiposity

Proteins secreted from adipose tissue are increasingly recognized to play an important role in the regulation of glucose metabolism. However, much less is known about their effect on lipid metabolism. The fasting-induced adipose factor (FIAF/angiopoietin-like protein 4/peroxisome proliferator-activated receptor gamma angiopoietin-related protein) was previously identified as a target of hypolipidemic fibrate drugs and insulin-sensitizing thiazolidinediones. Using transgenic mice that mildly overexpress FIAF in peripheral tissues we show that FIAF is an extremely powerful regulator of lipid metabolism and adiposity. FIAF overexpression caused a 50% reduction in adipose tissue weight, partly by stimulating fatty acid oxidation and uncoupling in fat. In addition, FIAF overexpression increased plasma levels of triglycerides, free fatty acids, glycerol, total cholesterol, and high density lipoprotein (HDL)-cholesterol. Functional tests indicated that FIAF overexpression severely impaired plasma triglyceride clearance but had no effect on very low density lipoprotein production. The effects of FIAF overexpression were amplified by a high fat diet, resulting in markedly elevated plasma and liver triglycerides, plasma free fatty acids, and plasma glycerol levels, and impaired glucose tolerance in FIAF transgenic mice fed a high fat diet. Remarkably, in mice the full-length form of FIAF was physically associated with HDL, whereas truncated FIAF was associated with low density lipoprotein. In human both full-length and truncated FIAF were associated with HDL. The composite data suggest that via physical association with plasma lipoproteins, FIAF acts as a powerful signal from fat and other tissues to prevent fat storage and stimulate fat mobilization. Our data indicate that disturbances in FIAF signaling might be involved in dyslipidemia.

Effect of acarbose on glucose homeostasis, lipogenesis and lipogenic enzyme gene expression in adipose tissue of weaned rats.

Acarbose is a potent intestinal glucosidase inhibitor which could have an anti-obesity property by reducing postprandial plasma glucose and insulin levels, potentially responsible for high rates of lipid synthesis in adipose tissue. We have tested this hypothesis by studying rats during the weaning period, when the lipogenic capacity of the adipose tissue develops. Rats were treated from age 19 days onwards with acarbose (10 mg/100 g diet) and studied at age 30 days. Acarbose was efficient in reducing postprandial excursions of both blood glucose and plasma insulin. Acarbose-treated rats behave like rats continuously infused with glucose with no metabolic signs of carbohydrate deprivation since gluconeogenesis was not activated. There was no massive caecal fermentation of carbohydrate since volatile fatty acids did not significantly increase in the portal blood. One of the most striking features of the acarbose-treated rats was the reduction of adipose tissue weight due to a reduced adipocyte size. This was concomitant with a reduced lipogenic capacity from glucose in isolated adipocytes under insulin stimulation. The activity of fatty acid synthase and acetyl-CoA carboxylase was decreased concomitantly with a reduced expression of their specific mRNA. This study allows the conclusion that postprandial hyperinsulinaemia and hyperglycaemia have a major role in the control of expression of lipogenic enzymes and thus on adipose tissue lipogenic capacity.

Lipogenèse des tissus adipeux de chevreaux sevrés à 4, 6 et 8 semaines

Adipose deposits and their lipogenic enzymes were studied on 27 young Alpine male kids. They were weaned either at 28, 42 or 56 days of age and for each age at weaning, 3 animals were slaughtered unweaned (P 0), or 14 (P + 14) or 56 (P +56) days after weaning. They received milk replacer ad libitum from day 5 after birth to weaning and concentrate, hay and water from a week before weaning to slaughter. The adipose tissues were very developed in the abdomen in P 0 and P + 56 animals. Subcutaneous tissues were scarce. All adipose tissues in the P + 14 were lighter. The older the animals, the greater was the reduction in adipose tissue weight between P 0 and P + 14. But this loss was proportionally higher in younger animals. In all P + 14 animals the perirenal tissues showed higher loss. Lipoprotein lipase (LPL) activity was high in abdominal adipose tissues of P 0 and P + 56 kids, particularly in the omental tissue, but was very low in sternal adipose tissue. LPL activity had a low value 14 days after weaning but its specific activity roughly reached the unweaned LPL value 56 days after weaning. By contrast, acetyl CoA carboxylase (ACX) activity was very low in omental adipose tissue but existed even in unweaned kids. Fifty-six days after weaning, this activity was high in 28-day weaned kids. The activity of both glucose-6-phosphate dehydrogenase (G6PDH) and malic enzyme (EM) was high in unweaned kids, particularly at 42 days. Surprisingly, EM activity was higher than G6PDH activity in kids weaned for 56 days. Thus, in ad libitum concentrate-fed kids, the ATP-citrate lyase EM pathway seemed to be active and important for lipogenesis.