Abdominal Adipocyte Size Research Articles

Adiposity Reduction by Cucumis melo var. gaettongchamoe Extract in High-Fat Diet-Induced Obese Mice.

This study investigated the anti-obesity effects of Cucumis melo var. gaettongchamoe (CG) in mice fed a high-fat diet (HFD). The mice received CG water extract (CGWE) treatment for 8 weeks, and changes in body weight and serum lipid levels were analyzed. The HFD + vehicle group showed a significant increase in body weight compared to the control group, while the HFD + CGWE and HFD + positive (orlistat) groups exhibited reduced body weight. Lipid profile analysis revealed lower levels of total cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein cholesterol in the HFD + CGWE group compared to the HFD + vehicle group. The HFD + vehicle group had increased abdominal fat weight and fat content, whereas both HFD + CGWE groups showed significant reductions in abdominal fat content and adipocyte size. Additionally, CGWE administration downregulated mRNA expression of key proteins involved in neutral lipid metabolism. CGWE also promoted hepatic lipolysis, reducing lipid droplet accumulation in hepatic tissue and altering neutral lipid metabolism protein expression. Furthermore, CGWE treatment reduced inflammatory mediators and suppressed the activation of the mitogen-activated protein kinase pathway in hepatic tissue. In conclusion, CGWE shows promise as a therapeutic intervention for obesity and associated metabolic dysregulation, including alterations in body weight, serum lipid profiles, adipose tissue accumulation, hepatic lipolysis, and the inflammatory response. CGWE may serve as a potential natural anti-obesity agent.

Diabetes and Insulin Resistance Show Association With Femoral Instead of Abdominal Adipocyte Size in Asian Indians

Objectives: Energy intake exceeding expenditure results in adipogenesis, which consists of adipocyte hyperplasia and hypertrophy. Adipocyte hypertrophy is the pathological hallmark of ‘sick fat’ responsible for the development of insulin resistance and diabetes mellitus. In Asian Indians, who show a thin, fat phenotype, the association of adipocyte hypertrophy in various fat depots with insulin resistance and diabetes is not precisely known. The objective of this study is to find an association between adipocyte size of abdominal and thigh fat depot and certain parameters of diabetes mellitus. Material & Methods: In this cross-sectional analytical study, 172 patients were recruited. Abdominal subcutaneous and visceral fat samples were available of 100 patients (Non-diabetics: 56; Diabetics: 44), whereas thigh fat was analyzed in 72 patients (Non-diabetics: 40; Diabetics: 32). All participants had a BMI of less than 30 kg/m2 to negate the effect of obesity on adipocyte size. Fasting glucose, insulin, HbA1c, lipid profile including triglycerides, and total cholesterol were measured in all participants, and HOMA-IR was calculated. Adipocyte size in biopsied tissue after fixation was measured with the help of Motic Panthera Moticam 5 trinocular microscope (BA210LED) and Adobe Photoshop CC image analysis tool. Results: Mean adipocyte size in abdominal visceral compartment in diabetics and non-diabetics were 16610.3 ± 889.5 um2 and 16129.8 ± 878.5 um2 respectively. Whereas, mean adipocyte size in abdominal subcutaneous fat in diabetics and non-diabetics were 15071.0 ± 1261.1 um2 and 14356.8 ± 1004.7 um2 respectively. Adipocyte size difference of both the abdominal compartments between diabetic and non-diabetic group was statistically non-significant (p= 0.70 & 0.65 in omental and abdominal subcutaneous compartments respectively). Mean adipocyte size of thigh in diabetics and non-diabetics were 13070.2 ± 1416.2 um2 and 9020.1 ± 811.1 um2 respectively and difference between adipocyte size between both groups was statistically significant (p = 0.01). Thigh Adipocyte size in diabetic subgroup was positively correlated with HOMA -IR (r = 0.4, p = 0.02), triglycerides (r= 0.4, p = 0.03), waist circumference (r = 0.32, p = 0.03). On multivariate linear regression analysis HOMA-IR (β= 0.45, p=0.00), triglycerides (β=0.38, p=0.01) and waist circumference (β=0.35, p=0.02) are predictor of increased adipocyte size. Conclusion: We found that thigh adipocyte size was significantly larger in diabetics in comparison to non-diabetics, whereas no such difference was found in the abdominal fat compartment. In diabetic patients’ thigh, adipocyte size was positively correlated with HOMA-IR, waist circumference, and triglyceride levels, underlining the role of peripheral fat depots in the pathogenesis of diabetes type 2.

PCBs–high-fat diet interactions as mediators of gut microbiota dysbiosis and abdominal fat accumulation in female mice

Polychlorinated biphenyls (PCBs), one type of lipophilic pollutant, are ubiquitous in daily life. PCBs exposure has been implicated in the alterations of gut microbial community which is profoundly associated with diverse metabolic disorders, including obesity. High-fat diet (H) is a dietary pattern characterized by a high percentage of fat. According to the theory that similarities can be easily solvable in each other, PCBs and H exposures are inevitably and objectively coexistent in a real living environment, prompting great concerns about their individual and combined effects on hosts. However, the effects of PCBs-H interactions on gut microbiota and obesity are still incompletely understood. In the present study, the effects of PCBs and/or H on the gut microbiota alteration and obesity risk in mice were examined and the interactions between PCBs and H were investigated. Obtained results showed that PCBs and/or H exposure induced prominent variations in the gut microbiota composition and diversity. Exposure to PCBs also resulted in higher body fat percentage, greater size of abdominal subcutaneous adipocytes and increased expression of proinflammatory cytokines including TNF-α, iNOS and IL-6. Such PCBs-induced changes could be further enhanced upon the co-exposure of H, implying that obese individuals may be vulnerable to PCBs exposure. Taken together, the present study is helpful for a better understanding of the gut microbiota variation influenced by PCBs and/or H exposure, and furthermore, provides a novel insight into the mechanism of PCBs-H interactions on host adiposity.

Abstract MP38: Effect of Dietary Carbohydrate Type on Serum Lipid Profile, Adipose Tissue Macrophage Infiltration and Inflammatory Status, and Peripheral Macrophage Cholesterol Efflux

Introduction: While much has been published on the effect of different amounts of dietary carbohydrate (carb) on cardiovascular disease (CVD) risk, data on effects of different types of carb (simple, refined and unrefined) are limited. Objective: To determine the relative comparability for an isocaloric replacement of unrefined-carb (UC; e.g., brown rice and bread/pasta made from whole wheat flour), refined-carb (RC; e.g., white rice and bread/pasta made from white flour) and simple-carb (SC; e.g., sucrose and high fructose corn syrup) on serum lipid and lipoprotein profile, adipose tissue gene expression of macrophage and inflammation markers, cytokine secretion and adipocyte size, and cholesterol efflux in peripheral blood mononuclear cells (PBMC). Methods: Study subjects (men and postmenopausal women [N=11], 65±8 y, BMI 29.8±3.2 kg/m 2 , LDL-C ≥2.6 mmol/L) were provided with isocaloric diets (60% E total carb, 15% E protein, 25% E fat) enriched in SC, RC or UC for 4.5 weeks, with a 2-week washout period between diet phases, using a randomized, cross-over design. Body weight was maintained within +/- 2 kg. At the end of each diet phase serum lipid and lipoprotein profile was determined using standard methods. Abdominal subcutaneous adipose tissue biopsies were collected and used to assess gene expression of macrophage and inflammation markers, cytokine secretion, and cell size. PBMCs were isolated and cultured to assess cholesterol efflux. Results: Fasting serum TC (p=0.004) and LDL-C (p=0.002) concentrations were higher after subjects consumed the RC diet than after the SC and UC diet phases. No significant differences were observed among diets in serum HDL-C (p=0.32), VLDL-C (p=0.17), TG (p=0.19), and NEFA (p=0.99) concentrations. Adipocyte size was largest after subjects consumed the RC diet and smallest after the SC diet (p<0.0001). There were no significant differences among diets in gene expression of the macrophage markers CD14 (p=0.62) and CD68 (p=0.62), and the inflammatory markers adiponectin (p=0.66), leptin (p=0.42), and IL-6 (p=0.92), except for a trend towards higher serum amyloid-1 expression after the RC diet (p=0.059). Inflammatory cytokine secretion of adiponectin (p=0.52), leptin (p=0.89), and IL-6 (p=0.07) were not significantly different among diet phases. No significant differences were observed in macrophage cholesterol efflux among diets (p=0.18). Conclusions: Consuming the RC diet resulted in higher serum TC and LDL-C concentrations, and concurrently increased abdominal subcutaneous adipocyte size. Dietary carb type had no significant effect on markers of macrophage infiltration, inflammation or cytokine secretion in adipose tissue, or macrophage cholesterol efflux. Results from this study provide mechanistic support for the epidemiologic findings that increasing consumption of RC diet is positively associated with CVD risk.

Abdominal subcutaneous and visceral adipocyte size, lipolysis and inflammation relate to insulin resistance in male obese humans

Obesity is associated with a disturbed adipose tissue (AT) function characterized by adipocyte hypertrophy, an impaired lipolysis and pro-inflammatory phenotype, which contributes to insulin resistance (IR). We investigated whether AT phenotype in different AT depots of obese individuals with and without type 2 diabetes mellitus (T2DM) is associated with whole-body IR. Subcutaneous (SC) and visceral (V) AT biopsies from 18 lean, 17 obese and 8 obese T2DM men were collected. AT phenotype was characterized by ex vivo measurement of basal and stimulated lipolysis (mature adipocytes), adipocyte size distribution (AT tissue sections) and AT immune cells (flow cytometry). In VAT, mean adipocyte size, CD45+ leukocytes and M1 macrophages were significantly increased in both obese groups compared to lean individuals. In SCAT, despite adipocyte hypertrophy, no significant differences in immune cell populations between groups were found. In SCAT, multiple linear regression analysis showed that none of the AT phenotype markers independently contributed to HOMA-IR while in VAT, mean adipocyte size was significantly related to HOMA-IR. In conclusion, beside adipocyte hypertrophy in VAT, M1 macrophage- or B-cell-mediated inflammation, may contribute to IR, while inflammation in hypertrophic SCAT does not seem to play a major role in IR.

Family history of type 2 diabetes, abdominal adipocyte size and markers of the metabolic syndrome.

Background/ObjectivesA major risk factor of type 2 diabetes mellitus (T2DM) is a positive family history of diabetes. First degree relatives (FDR) of patients with T2DM are more insulin resistant and are reported to have larger abdominal subcutaneous adipocytes than adults without a family history. Our objectives were to assess whether a family history of T2DM is associated with larger abdominal adipocytes independent of age, sex, and abdominal subcutaneous fat and to assess whether FDR of T2DM is also independently related to femoral adipocyte size, as well as visceral fat and fasting plasma triglyceride (TG) concentrations.MethodsWe extracted adipocyte size, body composition, plasma TG and demographic data of non-diabetic research participants of previous studies conducted in our laboratory. We ascertained the family history of T2DM from the electronic medical records. Multivariate regression analysis was used to assess whether FDR of T2DM are more likely to have other risk factors after adjusting for known covariates.ResultsOf 604 participants, 148 were a FDR of T2DM. Although abdominal and femoral adipocyte size was greater in FDR of T2DM than those without a family history (0.74 ± 0.33 vs 0.63 ± 0.33 µg lipid/cell, P < 0.001; 0.81 ± 0.29 vs 0.72 ± 0.33 µg lipid/cell, P=0.01, respectively), this was confounded by FDR of T2DM being older, having greater BMI’s and percent body fat. A family history of T2DM was a significant predictor of abdominal adipocyte size after adjustment for age and body fat distribution parameters in females (total R2=0.5, p < 0.0001), but not in males. A family history of T2DM was not independently predictive of femoral adipocyte size, visceral fat area or TG.ConclusionsFDR of T2DM females have larger abdominal, but not femoral, adipocytes, even after accounting for age and body fat distribution.

GH administration decreases subcutaneous abdominal adipocyte size in men with abdominal obesity

ObjectiveTo investigate the effects of short-term GH administration on abdominal subcutaneous adipocyte size and CT attenuation in men with abdominal obesity. Design6-week, randomized, double-blind, placebo-controlled study of GH (starting dose 2μg/kg/d) vs placebo of 15 abdominally obese men (mean age: 34±6years; mean BMI: 37.7±6.1kg/m2, mean IGF-1 SDS: −1.9±0.5) who underwent abdominal subcutaneous adipose tissue (SAT) aspirations to determine adipocyte size, CTs for body composition and measures of glucose tolerance at baseline and 6weeks. GH dosing was titrated to target IGF-1 levels in the upper normal age-appropriate range. ResultsGH administration decreased subcutaneous abdominal adipocyte size compared to placebo. Adipocyte size was positively associated with 120-min glucose and HOMA-IR and inversely associated with peak-stimulated GH and CT attenuation. CT attenuation of SAT was inversely associated with 120-min glucose and HOMA-IR and increased following GH administration. ConclusionIn men with abdominal obesity, subcutaneous abdominal adipocyte size is positively associated with measures of impaired glucose tolerance and administration of GH at doses that raise IGF-1 levels within the normal range, decreases abdominal subcutaneous adipocyte size, suggesting that GH administration improves the health of adipose tissue.Clinical trials number: NCT00131378

Incubation temperature manipulation during fetal development reduces adiposity of broiler hatchlings

Broilers are known as an efficient source of lean meat. Genetic selection resulted in broiler strains with large body size and fast growth, but a concomitant increase in fat deposition also occurred. Other than reducing nutrient intake, there is a lack of alternative methods to control body fat composition of broilers. The present study assessed whether incubation temperature (machine temperatures: 36ºC, 37.5ºC, and 39ºC; eggshell temperatures: 37.4 ± 0.08°C, 37.8 ± 0.15ºC, and 38.8 ± 0.33°C, respectively.) from d 13 affects broiler hatchling fat deposition. We analyzed adipocyte hypertrophy and proliferation in 3 body regions; weight and chemical composition of yolk-free chicks and yolk sacs; and serum lipid profile. Increased incubation temperature reduced abdominal and cervical adipocyte size. Independently of temperature, cervical adipocytes were smaller and showed higher proliferation than adipocytes in the abdominal and thigh regions. Smaller cervical adipocytes were observed in birds from eggs incubated at 36ºC and 39ºC. With regard to weight and composition of chicks, ash content as a percentage of dry matter was the only variable affected by temperature; it was higher in chicks from eggs incubated at 36ºC than at 39ºC and showed no significant difference between chicks incubated at 39ºC and 37.5ºC. Absolute and relative weights of yolk sacs were higher from eggs incubated at 39ºC than at 36ºC, and these two treatments did not differ from the 37.5ºC control. Absolute measures of yolk sac lipids, moisture, dry matter, and crude protein content were lower in chicks from eggs incubated at 36ºC, and no significant differences were found for these variables between chicks from eggs incubated at 37.5ºC and 39ºC. Hatchlings from eggs incubated at 36°C had significantly higher cholesterol levels than chicks incubated at the other 2 temperatures, but no additional effects on blood lipids were detected. Incubation temperature manipulation during fetal development altered cervical and abdominal adipocyte size in broiler hatchlings and could become a tool in hatcheries to manipulate chick quality, although further studies are needed to evaluate its long-term effects.

A Novel Letrozole Model Recapitulates Both the Reproductive and Metabolic Phenotypes of Polycystic Ovary Syndrome in Female Mice.

Polycystic ovary syndrome (PCOS) pathophysiology is poorly understood, due partly to lack of PCOS animal models fully recapitulating this complex disorder. Recently, a PCOS rat model using letrozole (LET), a nonsteroidal aromatase inhibitor, mimicked multiple PCOS phenotypes, including metabolic features absent in other models. Given the advantages of using genetic and transgenic mouse models, we investigated whether LET produces a similar PCOS phenotype in mice. Pubertal female C57BL/6N mice were treated for 5 wk with LET, which resulted in increased serum testosterone and normal diestrus levels of estradiol, similar to the hyperandrogenemia and follicular phase estrogen levels of PCOS women. As in PCOS, ovaries from LET mice were larger, polycystic, and lacked corpora lutea versus controls. Most LET females were acyclic, and all were infertile. LET females displayed elevated serum LH levels and higher Lhb mRNA in the pituitary. In contrast, serum FSH and Fshb were significantly reduced in LET females, demonstrating differential effects on gonadotropins, as in PCOS. Within the ovary, LET females had higher Cyp17, Cyp19, and Fsh receptor mRNA expression. In the hypothalamus, LET females had higher kisspeptin receptor mRNA expression but lower progesterone receptor mRNA levels. LET females also gained more weight than controls, had increased abdominal adiposity and adipocyte size, elevated adipose inflammatory mRNA levels, and impaired glucose tolerance, mirroring the metabolic phenotype in PCOS women. This is the first report of a LET paradigm in mice that recapitulates both reproductive and metabolic PCOS phenotypes and will be useful to genetically probe the PCOS condition.

Enriching the Diet In N‐3 Polyunsaturated Fatty Acids Reduces Adiposity and Adipocyte Size in a Broiler Chick Model for Childhood Obesity

Epidemiological studies suggest that enriching prenatal and perinatal diets in long‐chain omega‐3 polyunsaturated fatty acids (LC n‐3 PUFA) may be a tool with which to reduce adiposity, improve metabolic status and reduce the risk of childhood obesity. We used broiler chickens, which rapidly deposit adipose tissue post‐hatch and share a number of metabolic features with humans, to test the hypothesis that consumption of diets enriched in LC n‐3 PUFA during the early post‐hatch period of rapid adipose development reduces adiposity. From seven to 21 days of age,Cobb500 broiler chicks (n=10/group) were fed isocaloric diets formulated using either lard (primarily saturated), corn oil (primarily monounsaturated), flaxseed oil (PUFA, enriched in alpha linolenic acid (ALA, 18:3, n‐3)), or fish oil (PUFA, enriched in eicosapentaenoic acid (EPA, 20:5, n‐3) and docosahexaenoic acid (DHA, 22:6, n‐3)), each at 8% by weight. Abdominal fat pad weight, but not body weight, was significantly (p=0.0327) lower in birds fed the fish oil diet (21.3g±5.5) than those fed lard (26.7g±5.9), but did not differ in birds fed flax and corn‐oil based diets relative to lard. Fish oil also significantly reduced abdominal adipocyte size compared to all other diets (p&lt;0.05). Subcutaneous adipocyte size was significantly smaller in corn, flax and fish oil groups relative to lard (p&lt;0.05). Plasma non‐esterified fatty acid levels, as a reflection of lipolysis, increased in birds fed fish oil diets as compared to lard diets (p=0.0194). Collectively, our data suggest that altering the type of fatty acids consumed during childhood may attenuate adipose deposition and adipocyte size, which could have benefits in reducing childhood obesity.

Adipose tissue remodeling in a novel domestic porcine model of diet-induced obesity

ObjectiveTo establish and characterize a novel domestic porcine model of obesity.Design and MethodsFourteen domestic pigs were fed normal (lean, n=7) or high-fat/high-fructose diet (obese, n=7) for 16 weeks. Subcutaneous abdominal adipose tissue biopsies were obtained after 8, 12 and 16 weeks of diet, and pericardial adipose tissue after 16 weeks, for assessments of adipocyte size, fibrosis, and inflammation. Adipose tissue volume and cardiac function were studied with multi-detector computed-tomography, and oxygenation with magnetic resonance imaging. Plasma lipids profiles, insulin resistance, and markers of inflammation were evaluated.ResultsCompared with lean, obese pigs had elevated cholesterol and triglycerides levels, blood pressure, and insulin resistance. Both abdominal and pericardial fat volume increased after 16 weeks of obese. In abdominal subcutaneous adipose tissue, adipocyte size and both tumor necrosis factor (TNF)-α expression progressively increased. Macrophage infiltration showed in both abdominal and pericardial adipose tissues. Circulating TNF-α increased in obese only at 16 weeks. Compared with Lean, obese pigs had similar global cardiac function, but myocardial perfusion and oxygenation were significantly impaired.ConclusionA high-fat/high-fructose diet induces in domestic pigs many characteristics of metabolic syndrome, which is useful to investigate the effects of the obesity.

Adipocyte morphology and implications for metabolic derangements in acquired obesity

Adipocyte size and number have been suggested to predict the development of metabolic complications in obesity. However, the genetic and environmental determinants behind this phenomenon remain unclear. We studied this question in rare-weight discordant (intra-pair difference (Δ) body mass index (BMI) 3-10 kg m(-2), n=15) and concordant (ΔBMI 0-2 kg m(-)(2), n=5) young adult (22-35 years) monozygotic twin pairs identified from 10 birth cohorts of Finnish twins (n=5 500 pairs). Subcutaneous abdominal adipocyte size from surgical biopsies was measured under a light microscope. Adipocyte number was calculated from cell size and total body fat (D × A). The concordant pairs were remarkably similar for adipocyte size and number (intra-class correlations 0.91-0.92, P<0.01), suggesting a strong genetic control of these measures. In the discordant pairs, the obese co-twins (BMI 30.6 ± 0.9 kg m(-2)) had significantly larger adipocytes (volume 547 ± 59 pl), than the lean co-twins (24.9 ± 0.9 kg m(-)(2); 356 ± 34 pl, P<0.001). In 8/15 pairs, the obese co-twins had less adipocytes than their co-twins. These hypoplastic obese twins had significantly higher liver fat (spectroscopy), homeostatic model assessment-index, C-reactive protein and low-density lipoprotein cholesterol than their lean co-twins. Hyperplastic obesity was observed in the rest (7/15) of the pairs, obese and lean co-twins having similar metabolic measures. In all pairs, Δadipocyte volume correlated positively and Δcell number correlated negatively with Δhomeostatic model assessment-index and Δlow-density lipoprotein, independent of Δbody fat. Transcripts most significantly correlating with Δadipocyte volume were related to a reduced mitochondrial function, membrane modifications, to DNA damage and cell death. Together, hypertrophy and hypoplasia in acquired obesity are related to metabolic dysfunction, possibly through disturbances in mitochondrial function and increased cell death within the adipose tissue.

Dietary Conjugated Linoleic Acid Supplementation Leads to Downregulation of PPAR Transcription in Broiler Chickens and Reduction of Adipocyte Cellularity.

Conjugated linoleic acids (CLA) act as an important ligand for nuclear receptors in adipogenesis and fat deposition in mammals and avian species. This study aimed to determine whether similar effects are plausible on avian abdominal fat adipocyte size, as well as abdominal adipogenic transcriptional level. CLA was supplemented at different levels, namely, (i) basal diet without CLA (5% palm oil) (CON), (ii) basal diet with 2.5% CLA and 2.5% palm oil (LCLA), and (iii) basal diet with 5% CLA (HCLA).The content of cis-9, trans-11 CLA was between 1.69- and 2.3-fold greater (P < 0.05) than that of trans-10, cis-12 CLA in the abdominal fat of the LCLA and HCLA group. The adipogenic capacity of the abdominal fat depot in LCLA and HCLA fed chicken is associated with a decreased proportion of adipose cells and monounsaturated fatty acids (MUFA). The transcriptional level of adipocyte protein (aP2) and peroxisome proliferator-activated receptor gamma (PPARγ) was downregulated by 1.08- to 2.5-fold in CLA supplemented diets, respectively. It was speculated that feeding CLA to broiler chickens reduced adipocyte size and downregulated PPARγ and aP2 that control adipocyte cellularity. Elevation of CLA isomers into their adipose tissue provides a potential CLA-rich source for human consumption.

Selenium Significantly Inhibits Adipocyte Hypertrophy and Abdominal Fat Accumulation in OLETF Rats via Induction of Fatty Acid β-Oxidation

A combination of selenium (Se) with other trace element is associated with partially modulate fatty acid distribution as well as reduction of the body weight and feed efficiency. To investigate whether or not Se treatment has an impact on lipid metabolism, we examined the levels of lipid metabolism-related factors, including abdominal fat, adiponectin, cholesterol, very long chain dehydrogenase (VLCAD), and medium chain acyl-CoA dehydrogenase (MCAD) in 20-week-old Otsuka Long-Evans Tokushima Fatty (OLETF) rats following sodium selenite treatment for 2weeks. Herein, we observed that (a) Se treatment induced insulin-like effects by lowering the serum glucose level in rats; (b) Se-treated rats showed significance values decreases in abdominal fat mass, adipocyte size, and adiponectin, which are associated with lipid metabolism; (c) Se treatment led to reduced levels of cholesterol, triglycerides, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol; (d) fat tissue in Se-treated rats displayed significantly lower expression of adipocyte marker genes along with increased expression of VLCAD and MCAD; and (e) fatty liver formation and β-oxidation gene expression were both significantly reduced in liver tissue of Se-treated rats. Therefore, our results suggest that Se may induce inhibition of adipocyte hypertrophy and abdominal fat accumulation along with suppression of fatty liver formation by the differential regulation of the gene expression for fatty acid β-oxidation in the OLETF model.

Effects of weight gain and weight loss on regional fat distribution

Normal-weight adults gain lower-body fat via adipocyte hyperplasia and upper-body subcutaneous (UBSQ) fat via adipocyte hypertrophy. We investigated whether regional fat loss mirrors fat gain and whether the loss of lower-body fat is attributed to decreased adipocyte number or size. We assessed UBSQ, lower-body, and visceral fat gains and losses in response to overfeeding and underfeeding in 23 normal-weight adults (15 men) by using dual-energy X-ray absorptiometry and abdominal computed tomography scans. Participants gained ∼5% of weight in 8 wk and lost ∼80% of gained fat in 8 wk. We measured abdominal subcutaneous and femoral adipocyte sizes and numbers after weight gain and loss. Volunteers gained 3.1 ± 2.1 (mean ± SD) kg body fat with overfeeding and lost 2.4 ± 1.7 kg body fat with underfeeding. Although UBSQ and visceral fat gains were completely reversed after 8 wk of underfeeding, lower-body fat had not yet returned to baseline values. Abdominal and femoral adipocyte sizes, but not numbers, decreased with weight loss. Decreases in abdominal adipocyte size and UBSQ fat mass were correlated (ρ = 0.76, P = 0.001), as were decreases in femoral adipocyte size and lower-body fat (ρ = 0.49, P = 0.05). UBSQ and visceral fat increase and decrease proportionately with a short-term weight gain and loss, whereas a gain of lower-body fat does not relate to the loss of lower-body fat. The loss of lower-body fat is attributed to a reduced fat cell size, but not number, which may result in long-term increases in fat cell numbers.

Valsartan Improves Adipose Tissue Function in Humans with Impaired Glucose Metabolism: A Randomized Placebo-Controlled Double-Blind Trial

BackgroundBlockade of the renin-angiotensin system (RAS) reduces the incidence of type 2 diabetes mellitus. In rodents, it has been demonstrated that RAS blockade improved adipose tissue (AT) function and glucose homeostasis. However, the effects of long-term RAS blockade on AT function have not been investigated in humans. Therefore, we examined whether 26-wks treatment with the angiotensin II type 1 receptor blocker valsartan affects AT function in humans with impaired glucose metabolism (IGM).Methodology/Principal FindingsWe performed a randomized, double-blind, placebo-controlled parallel-group study, in which 38 subjects with IGM were treated with valsartan (VAL, 320 mg/d) or placebo (PLB) for 26 weeks. Before and after treatment, an abdominal subcutaneous AT biopsy was collected for measurement of adipocyte size and AT gene/protein expression of angiogenesis/capillarization, adipogenesis, lipolytic and inflammatory cell markers. Furthermore, we evaluated fasting and postprandial AT blood flow (ATBF) (133Xe wash-out), systemic inflammation and insulin sensitivity (hyperinsulinemic-euglycemic clamp). VAL treatment markedly reduced adipocyte size (P<0.001), with a shift toward a higher proportion of small adipocytes. In addition, fasting (P = 0.043) and postprandial ATBF (P = 0.049) were increased, whereas gene expression of angiogenesis/capillarization, adipogenesis and macrophage infiltration markers in AT was significantly decreased after VAL compared with PLB treatment. Interestingly, the change in adipocyte size was associated with alterations in insulin sensitivity and reduced AT gene expression of macrophage infiltration markers. VAL did not alter plasma monocyte-chemoattractant protein (MCP)-1, TNF-α, adiponectin and leptin concentrations.Conclusions/Significance26-wks VAL treatment markedly reduced abdominal subcutaneous adipocyte size and AT macrophage infiltration markers, and increased ATBF in IGM subjects. The VAL-induced decrease in adipocyte size was associated with reduced expression of macrophage infiltration markers in AT. Our findings suggest that interventions targeting the RAS may improve AT function, thereby contributing to a reduced risk of developing cardiovascular disease and type 2 diabetes.Trial RegistrationTrialregister.nl NTR721 (ISRCTN Registry: ISRCTN42786336)

Abstract 440: Regional Differences in Fat Loss Following Weight Gain in Normal Adults

Background: Normal weight adults gain leg fat gain via adipocyte hyperplasia and upper body subcutaneous (UBSQ) fat gain via adipocyte hypertrophy. Objective: To understand whether regional fat loss mirrors fat gain and whether leg fat loss results in decreased adipocyte number vs. size. Design: We assessed UBSQ, leg and visceral fat gain and loss in response to over- and underfeeding in 23 young, healthy normal weight adults (15 men). Participants gained ∼5% weight over 8 weeks and lost ∼80% of gained fat over the following 8 weeks. We measured abdominal subcutaneous and femoral adipocyte size and number after weight gain and loss. Results: Volunteers gained 3.1 ± 2.1 kg of body fat with overfeeding and lost 2.4 ± 1.7 kg with calorie restriction. Although upper body subcutaneous (UBSQ) fat and visceral fat gains were completely reversed with weight loss, leg fat had not yet returned to baseline values by 8 weeks. Abdominal and femoral adipocyte size decreased significantly with weight loss, but the number of adipocytes did not decrease. Abdominal adipocyte size decreases correlated (rho= 0.76, p = 0.001) with UBSQ fat mass decreases and femoral adipocyte size decreases correlated (rho= 0.49, p=0.05) with leg fat mass decreases. Conclusion: UBSQ and visceral fat depots increase and decrease proportionately with short term weight gain and loss, whereas gain and loss of leg fat are less well linked. Loss of lower body fat is due to reduced fat cell size, not number, which may result in long-term increases in leg fat cell number. This may have implications for long-term weight control.

Combined deficiency of the CB1 and CB2 receptors enhances peak bone mass by inhibiting osteoclast differentiation but increases age-related bone loss by promoting adipocyte differentiation and reducing osteoblast differentiation

Combined deficiency of the CB1 and CB2 receptors enhances peak bone mass by inhibiting osteoclast differentiation but increases age-related bone loss by promoting adipocyte differentiation and reducing osteoblast differentiation

Anti-obesity effects of Rapha diet® preparation in mice fed a high-fat diet.

The anti-obesity activities of Rapha diet® preparation containing silkworm pupa peptide, Garcinia cambogia, white bean extract, mango extract, raspberry extract, cocoa extract, and green tea extract were investigated in mice with dietary obesity. Male C57BL/6 mice were fed a high-fat diet (HFD) containing 3% Rapha diet® preparation for 8 weeks, and blood and tissue parameters of obesity were analyzed. The HFD markedly enhanced body weight gain by increasing the weights of epididymal, perirenal, and mesenteric adipose tissues. The increased body weight gain induced by HFD was significantly reduced by feeding Rapha diet® preparation, in which decreases in the weight of abdominal adipose tissue and the size of abdominal adipocytes were confirmed by microscopic examination. Long-term feeding of HFD increased blood triglycerides and cholesterol levels, leading to hepatic lipid accumulation. However, Rapha diet® preparation not only reversed the blood lipid levels, but also attenuated hepatic steatosis. The results indicate that Rapha diet® preparation could improve HFD-induced obesity by reducing both lipid accumulation and the size of adipocytes.

Estrogen modulates abdominal adiposity and protects female mice from obesity and impaired glucose tolerance

Obesity increases the risk of diabetes. The dysregulation of estrogen metabolism has been associated with the susceptibility to obesity and diabetes. Here, we explore the role estrogen plays in sex differences in obesity and glucose metabolism, specifically adipocyte biology. We randomized C57BL/6 J male, non-ovariectomized female, ovariectomized female, and ovariectomized female mice supplemented with 17β estradiol to receive a calorie-restricted, low- or a high-fat diet (15 mice per group). We measured weight gained, calories consumed, percent body fat, abdominal adipose tissue, adipocyte size, lipogenic and adipogenic gene expression, and glucose tolerance. Male mice had a higher susceptibility to obesity than intact female mice. However, removal of the ovaries in female mice eliminated the protection to obesity and estrogen supplementation restored this protection. Male and ovariectomized female mice gained weight predominately in the form of abdominal adipose tissue possibly due to an increase in adipocyte size. Moreover, for mice consuming the high-fat diet, male and ovariectomized female mice had significantly higher levels of leptin mRNA and lower hormone-sensitive lipase mRNA relative to intact female mice and ovariectomized female mice supplemented with estrogen. Additionally, estrogen had a strong inhibitory effect on key adipogenic genes in non-ovariectomized female and ovx-female mice supplemented with estrogen. Finally, we show that male and ovariectomized female mice consuming the high-fat diet had a higher incidence of glucose intolerance. Estrogen protects female mice from obesity and impaired glucose tolerance possibly by modulating the expression of genes regulating adipogenesis, lipogenesis, and lipolysis.