Sex‐ and Depot‐Dependent Differences in Adipogenesis in Normal‐Weight Humans

To elucidate cellular mechanisms of sex‐related differences in fat distribution, we determined body fat distribution (dual‐energy X‐ray absorptiometry and single‐slice abdominal computed tomography (CT)), adipocyte size, adipocyte number, and proportion of early‐differentiated adipocytes (aP2⁺CD68^?) in the stromovascular fraction (SVF) in the upper and lower body of normal‐weight healthy men (n = 12) and premenopausal women (n = 20) (age: 18–49 years, BMI: 18–26 kg/m²). Women had more subcutaneous and less visceral fat than men. The proportion of early differentiated adipocytes in the subcutaneous adipose tissue SVF of women was greater than in men (P = 0.01), especially in the femoral depot, although in vitro adipogenesis, as assessed by peroxisome proliferator activated receptor‐γ (PPARγ) expression, was not increased in femoral preadipocytes cultured from women compared with men. In women, differentiation of femoral preadipocytes was less than that of abdominal subcutaneous preadipocytes (P = 0.04), and femoral subcutaneous preadipocytes tended to be more resistant to tumor necrosis factor‐α (TNFα)–induced apoptosis (P = 0.06). Thus, turnover and utilization of the preadipocyte pool may be reduced in lower vs. the upper‐body fat in women. Collectively, these data indicate that the microenvironment, rather than differences in inherent properties of preadipocytes between genders, may explain the gynoid obesity phenotype and higher percent body fat in women compared to men.     

Relation of epicardial fat and alanine aminotransferase in subjects with increased visceral fat

Background: Increased visceral adipose tissue (VAT) is a risk factor for an unfavorable cardio‐metabolic profile and fatty liver. Individuals with human immunodeficiency virus (HIV) on highly active antiretroviral therapy (HAART) can be associated with metabolic syndrome (MS) and higher visceral fat. However, the potential link between cardiac adiposity, emerging index of visceral adiposity, and fatty liver is still unexplored. Objective: To evaluate whether echocardiographic epicardial adipose tissue, index of cardiac adiposity, could be related to serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity, surrogate markers of fatty liver, in HIV‐infected patients with (HIV+MS+) and without HAART‐associated MS (HIV+MS‐). Methods and Procedures: This was a cross‐sectional observational study on 57 HIV+MS+ patients, 52 HIV+MS? and 57 HIV‐negative subjects with MS (HIV?MS+), as control group. Epicardial fat thickness and intra‐abdominal VAT were obtained by echocardiography and magnetic resonance imaging (MRI), respectively. Serum ALT and AST activity, plasma adiponectin levels, and MS biochemical parameters were measured. Results: Echocardiographic epicardial fat thickness was correlated with MRI‐VAT (r = 0.83, P < 0.01), AST/ALT ratio (r = 0.77, P < 0.01), ALT (r = 0.58, P < 0.01), AST (r = 0.56, P < 0.01), and adiponectin (r = ?0.45, P < 0.01) in HIV+MS+. MRI‐VAT and AST/ALT ratio were the best correlates of epicardial fat thickness (r ² = 0.45, P < 0.01). Discussion: This study shows for the first time a clear relationship of epicardial fat, index of cardiac and visceral adiposity, and serum ALT and AST activity, markers of fatty liver, in subjects with increased visceral adiposity and cardio‐metabolic risk. This correlation seems to be independent of overall adiposity and rather function of excess visceral adiposity.     

Comparison of three bioelectrical impedance methods with DXA in overweight and obese men

Objective: To compare bioelectrical impedance analysis (BIA) of body composition using three different methods against DXA in overweight and obese men. Research Methods and Procedures: Forty‐three healthy overweight or obese men (ages 25 to 60 years; BMI, 28 to 43 kg/m²) underwent BIA assessment of body composition using the ImpediMed SFB7 (version 6; ImpediMed, Ltd., Eight Mile Plains, Queensland, Australia) in multifrequency mode (Imp‐MF) and DF50 single‐frequency mode (Imp‐SF) and the Tanita UltimateScale (Tanita Corp., Tokyo, Japan). Validity was assessed by comparison against DXA using linear regression and limits of agreement analysis. Results: All three BIA methods showed good relative agreement with DXA [Imp‐MF: fat mass (FM), r² = 0.81; fat‐free mass (FFM), r² = 0.81; percentage body fat (BF%), r² = 0.69; Imp‐SF: FM, r² = 0.65; FFM, r² = 0.76; BF%, r² = 0.40; Tanita: BF%, r² = 0.44; all p < 0.001]. Absolute agreement between DXA and Imp‐MF was poor, as indicated by a large bias and wide limits of agreement (bias, ±1.96 standard deviation; FM, ?6.6 ± 7.7 kg; FFM, 8.0 ± 7.1 kg; BF%, ?7.0 ± 6.6%). Imp‐SF and Tanita exhibited a smaller bias but wide limits of agreement (Imp‐SF: FM, ?1.1 ± 8.5 kg; FFM, 2.5 ± 7.9 kg; BF%, ?1.7 ± 7.3% Tanita: BF%, 1.2 ± 9.5%). Discussion: Compared with DXA, Imp‐MF produced large bias and wide limits of agreement, and its accuracy estimating body composition in overweight or obese men was poor. Imp‐SF and Tanita demonstrated little bias and may be useful for group comparisons, but their utility for assessment of body composition in individuals is limited.     

Depot-specific effects of the PPAR�� agonist rosiglitazone on adipose tissue glucose uptake and metabolism

We investigated mechanisms whereby peroxisome proliferator-activated receptor γ (PPARγ) agonism redistributes lipid from visceral (VF) toward subcutaneous fat (SF) by studying the impact of PPARγ activation on VF and SF glucose uptake and metabolism, lipogenesis, and enzymes involved in triacylglycerol (TAG) synthesis. VF (retroperitoneal) and SF (inguinal) of rats treated or not for 7 days with rosiglitazone (15 mg/kg/day) were evaluated in vivo for glucose uptake and lipogenesis and in vitro for glucose metabolism, gene expression, and activities of glycerolphosphate acyltransferase (GPAT), phosphatidate phosphatase-1 (or lipin-1), and diacylglycerol acyltransferase. Rosiglitazone increased SF glucose uptake, GLUT4 mRNA, and insulin-stimulated glucose oxidation, conversion to lactate, glycogen, and the glycerol and fatty acid components of TAG. In VF, only glucose incorporation into TAG-glycerol was stimulated by rosiglitazone and less so than in SF (1.5- vs. 3-fold). mRNA levels of proteins involved in glycolysis, Krebs cycle, glycogen synthesis, and lipogenesis were markedly upregulated by rosiglitazone in SF and again less so in VF. Rosiglitazone activated TAG-glycerol synthesis in vivo (2.8- vs. 1.9-fold) and lipin activity (4.6- vs. 1.5-fold) more strongly in SF than VF, whereas GPAT activity was increased similarly in both depots. The preferential increase in glucose uptake and intracellular metabolism in SF contributes to the PPARγ-mediated redistribution of TAG from VF to SF, which in turn favors global insulin sensitization.     

CD36 is important for adipocyte recruitment and affects lipolysis

Objective: The scavenger receptor CD36 facilitates the cellular uptake of long‐chain fatty acids. As CD36‐deficiency attenuates the development of high fat diet (HFD)‐induced obesity, the role of CD36‐deficiency in preadipocyte recruitment and adipocyte function was set out to characterize. Design and Methods: Fat cell size and number were determined in gonadal, visceral, and subcutaneous adipose tissue of CD36^?/? and WT mice after 6 weeks on HFD. Basal lipolysis and insulin‐inhibited lipolysis were investigated in gonadal adipose tissue. Results: CD36^?/? mice showed a reduction in adipocyte size in all fat pads. Gonadal adipose tissue also showed a lower total number of adipocytes because of a lower number of very small adipocytes (diameter <50 μm). This was accompanied by an increased pool of preadipocytes, which suggests that CD36‐deficiency reduces the capacity of preadipocytes to become adipocytes. Regarding lipolysis, in adipose tissue from CD36^?/? mice, cAMP levels were increased and both basal and 8‐bromo‐cAMP stimulated lipolysis were higher. However, insulin‐mediated inhibition of lipolysis was more potent in CD36^?/? mice. Conclusions: These results indicate that during fat depot expansion, CD36‐deficiency negatively affects preadipocyte recruitment and that in mature adipocytes, CD36‐deficiency is associated with increased basal lipolysis and insulin responsiveness.     

The Associations of LPIN1 Gene Expression in Adipose Tissue With Metabolic Phenotypes in the Chinese Population

The LPIN1 gene, encoding lipin‐1 protein, plays critical roles in adipocyte differentiation and lipid metabolism. This study aimed to analyze the association of LPIN1 mRNA levels in human adipose tissue with metabolic phenotypes. We also examined the association of LPIN1 genetic variation with type 2 diabetes and related metabolic phenotypes in the Chinese population. The relative LPIN1 mRNA levels were measured in abdominal visceral (VAT) and subcutaneous adipose tissue (SAT) obtained from 102 nondiabetic Chinese females. Seven single‐nucleotide polymorphisms (SNPs) spanning from the 5′‐upstream region to the 3′‐end of the LPIN1 gene were genotyped in 1,520 Chinese (760 type 2 diabetic cases and 760 controls). LPIN1 mRNA levels in VAT were negatively correlated with BMI (r = ?0.21, P = 0.03), body fat percentage (r = ?0.22, P = 0.02), plasma triglycerides levels (r = ?0.21, P = 0.03), and plasma leptin levels (r = ?0.63, P = 0.0002). LPIN1 mRNA levels were positively correlated with PPARG and ADIPOQ mRNA levels in both VAT and SAT. No single SNP of the LPIN1 gene was associated with type 2 diabetes in our population. One rare haplotype showed a significant association with type 2 diabetes (odds ratio (OR), 4.35; 95% confidence interval, 1.86–11.75; P = 4 × 10^?4). No SNP or haplotype of the LPIN1 gene was associated with quantitative metabolic traits in the nondiabetic subjects. The results confirmed the association of LPIN1 gene expression in adipose tissue with lower adiposity and favorable metabolic profiles in the Chinese population. However, the LPIN1 gene seemed not to be a major susceptibility gene for type 2 diabetes or related metabolic phenotypes in the Chinese population.     

Adipocytes IGFBP‐2 Expression in Prepubertal Obese Children

Aims of the study were to measure insulin‐like growth factor‐binding protein‐2 (IGFBP‐2) expression by abdominal subcutaneous adipocytes and to assess the relationship between IGFBP‐2 expression, circulating IGFBP‐2, obesity, and insulin sensitivity in obese children. Thirty‐eight obese children were recruited. Insulin sensitivity was assessed by intravenous glucose tolerance test and body composition by total‐body dual‐energy X‐ray absorptiometry. Serum free and total IGF‐I, IGFBP‐2, adiponectin, and leptin were measured. Relative quantification of IGFBP‐2 mRNA by subcutaneous adipose tissue biopsies was obtained using real‐time PCR. Circulating IGFBP‐2 was positively associated with insulin sensitivity, in agreement with previous studies. IGFBP‐2 expression was associated with fat mass percentage (r = 0.656; P < 0.02), insulin sensitivity (r = ?0.604; P < 0.05), free IGF‐I (r = 0.646; P < 0.05), and leptin (r = 0.603; P < 0.05), but not with circulating IGFBP‐2 (r = 0.003, P = ns). The association between IGFBP‐2 expression and adiposity (r = 0.648; P < 0.05) was independent of insulin sensitivity (covariate). In conclusion, circulating IGFBP‐2 was positively associated with insulin sensitivity. IGFBP‐2 was expressed by subcutaneous abdominal adipocytes of obese children and increased with adiposity, independently from the level of insulin sensitivity. IGFBP‐2 expression may potentially be one of the local mechanisms used by adipocytes to limit further fat gain.     

Lifelong reduction in complex IV induces tissue‐specific metabolic effects but does not reduce lifespan or healthspan in mice

Loss of SURF1, a Complex IV assembly protein, was reported to increase lifespan in mice despite dramatically lower cytochrome oxidase (COX) activity. Consistent with this, our previous studies found advantageous changes in metabolism (reduced adiposity, increased insulin sensitivity, and mitochondrial biogenesis) in Surf1^?/? mice. The lack of deleterious phenotypes in Surf1^?/? mice is contrary to the hypothesis that mitochondrial dysfunction contributes to aging. We found only a modest (nonsignificant) extension of lifespan (7% median, 16% maximum) and no change in healthspan indices in Surf1^?/? vs. Surf1^+/+ mice despite substantial decreases in COX activity (22%–87% across tissues). Dietary restriction (DR) increased median lifespan in both Surf1^+/+ and Surf1^?/? mice (36% and 19%, respectively). We measured gene expression, metabolites, and targeted expression of key metabolic proteins in adipose tissue, liver, and brain in Surf1^+/+ and Surf1^?/? mice. Gene expression was differentially regulated in a tissue‐specific manner. Many proteins and metabolites are downregulated in Surf1^?/? adipose tissue and reversed by DR, while in brain, most metabolites that changed were elevated in Surf1^?/? mice. Finally, mitochondrial unfolded protein response (UPR^mt)‐associated proteins were not uniformly altered by age or genotype, suggesting the UPR^mt is not a key player in aging or in response to reduced COX activity. While the changes in gene expression and metabolism may represent compensatory responses to mitochondrial stress, the important outcome of this study is that lifespan and healthspan are not compromised in Surf1^?/? mice, suggesting that not all mitochondrial deficiencies are a critical determinant of lifespan.     

Relative contributions of adiposity and muscularity to physical function in community-dwelling older adults

Objective: To determine the relative contributions of adiposity and muscularity to multi‐dimensional performance‐based and perceived physical function in older adults living independently. Methods and Procedures: Data from 109 women and men, aged 60 or older, with low serum dehydroepiandrosterone (DHEA) sulfate levels were included in this cross‐sectional analysis of baseline measures from a single‐site, randomized, controlled trial of DHEA replacement therapy. Physical function was determined by means of performance on the 100‐point Continuous Scale‐Physical Functional Performance (CS‐PFP) test and by self‐reporting using the physical function subscale of the Medical Outcomes Short Form‐36 (SF36_PF). Body composition was measured by dual‐energy X‐ray absorptiometry (DXA). Linear regression analyses were used to determine the contributions of body mass index (BMI; kg body mass/m²), fat index (FI; kg fat/m²), and appendicular skeletal muscle index (ASMI; kg muscle/m²) to the CS‐PFP and SF36_PF scores, adjusted for age and sex. Results: Age‐adjusted regression analyses indicated that FI, but not ASMI, was a significant (P < 0.001) determinant of CS‐PFP (R ² = 0.54) and SF36_PF (R ² = 0.37). When adjusted for age and sex, BMI was nearly as good a predictor of CS‐PFP (R ² = 0.50) and SF36_PF (R ² = 0.34) as FI. Discussion: Adiposity was a stronger predictor of measured and self‐reported physical function than was muscularity in older adults living independently. BMI, adjusted for sex, is a reasonable substitute for adiposity in the prediction of physical function.     

Circulating IL-6 concentrations and abdominal adipocyte isoproterenol-stimulated lipolysis in women

Objective: To examine the association of plasma interleukin‐6 (IL‐6) concentrations with adiposity and fat cell metabolism in women. Methods and Procedures: Omental (OM) and subcutaneous (SC) adipose tissue samples were obtained from 48 healthy women (age: 47 ± 5 years, BMI: 26.9 ± 5.3 kg/m²) undergoing gynecological surgeries. Total and visceral adiposity were assessed by dual‐energy X‐ray absorptiometry and computed tomography, respectively. Measures of adipocyte lipolysis (basal, isoproterenol‐, forskolin‐, and cyclic dibutyryl‐adenosine monophosphate (AMP)‐stimulated) and adipose tissue lipoprotein lipase (LPL) activity were obtained. Plasma IL‐6 was measured by radioimmunoassay. Results: Plasma IL‐6 was positively correlated with total body fat mass (r = 0.32, P < 0.05), SC adipose tissue area (r = 0.35, P < 0.05), SC adipocyte diameter (r = 0.30, P < 0.05), and a trend was observed with visceral adipose tissue area (r = 0.20, P < 0.07). Plasma IL‐6 was positively correlated with glycerol released in response to isoproterenol (10^?5 to 10^?8 mol/l) by isolated SC (0.31 ≤ r ≤ 0.65, P < 0.05) and OM (0.36 ≤ r ≤ 0.40, P < 0.02) adipocytes, independent of menopausal status. No correlation was found with LPL activity. A subsample of women with high plasma IL‐6 (n = 10) was matched with women with low plasma IL‐6 (n = 10) for total body fat mass. OM adipocyte glycerol release in response to isoproterenol (10^?5 to 10^?8 mol/l) was higher in the subsample of women with elevated plasma IL‐6 (P ≤ 0.07). Discussion: We observed that OM lipolysis was significantly higher in women with elevated plasma IL‐6 for a similar body fat mass and menopausal status. These results suggest that higher circulating IL‐6 concentrations are associated with increased isoproterenol‐stimulated lipolysis especially in OM abdominal adipocytes in women.     

Body composition of obese subjects by air displacement plethysmography: The influence of hydration

Objective: We investigated whether air displacement plethysmography (ADP) could detect small changes in body composition of obese subjects with alterations in hydration. Research Methods and Procedures: Ten obese subjects (mean BMI, 39.3 ± 2.8 kg/m²) entered the ADP chamber without and with oil (1, 2, or 4 liters), water (1, 2, or 4 liters), or mixed (1 liter oil + 1 liter water or 2 liters oil + 2 liters water) loads. Real and measured changes in body composition were compared by regression analysis and Bland‐Altman procedures. Results: The ADP‐measured changes in volume did not differ from the real values and were strongly correlated with them (r = 0.98). In all cases, loads of differing composition and similar volume led to different values of fat, fat‐free mass, and percentage fat. Water was detected as increased fat‐free mass only with loads of ≥2 liters, most of the water being falsely detected as increased fat mass. The observed changes were correlated with the real ones for fat mass (r = 0.68; p < 0.0001), fat‐free mass (r = 0.66; p < 0.0001), and percentage fat (r = 0.61; p < 0.0001), but fat mass changes were overestimated by ～1 kg, and fat‐free mass changes were underestimated by ～1 kg. This underestimation increased with the highest water loads, as shown by the Bland‐Altman plot (r = ?0.27; p < 0.05). Percentage fat changes were overestimated by 0.8% (p < 0.001); the magnitude of the error was correlated with the weight of the water load (r = 0.62; p < 0.0001). Discussion: ADP accurately measures changes in body volume, discriminating small changes in body composition. It overestimates changes in adiposity, as most of the increased hydration is detected as an enlarged fat mass.     

Association of Pericardial Fat With Liver Fat and Insulin Sensitivity After Diet‐Induced Weight Loss in Overweight Women

Pericardial adipose tissue (PAT) is positively associated with fatty liver and obesity‐related insulin resistance. Because PAT is a well‐known marker of visceral adiposity, we investigated the impact of weight loss on PAT and its relationship with liver fat and insulin sensitivity independently of body fat distribution. Thirty overweight nondiabetic women (BMI 28.2–46.8 kg/m², 22–41 years) followed a 14.2 ± 4‐weeks low‐calorie diet. PAT, abdominal subcutaneous (SAT), and visceral fat volumes (VAT) were measured by magnetic resonance imaging (MRI), total fat mass, trunk, and leg fat by dual‐energy X‐ray absorptiometry and intrahepatocellular lipids (IHCL) by (¹)H‐magnetic resonance spectroscopy. Euglycemic hyperinsulinemic clamp (M) and homeostasis model assessment of insulin resistance (HOMA_IR) were used to assess insulin sensitivity or insulin resistance. At baseline, PAT correlated with VAT (r = 0.82; P < 0.001), IHCL (r = 0.46), HOMA_IR (r = 0.46), and M value (r = ?0.40; all P < 0.05). During intervention, body weight decreased by ?8.5%, accompanied by decreases of ?12% PAT, ?13% VAT, ?44% IHCL, ?10% HOMA2‐%B, and +24% as well as +15% increases in HOMA2‐%S and M, respectively. Decreases in PAT were only correlated with baseline PAT and the loss in VAT (r = ?0.56; P < 0.01; r = 0.42; P < 0.05) but no associations with liver fat or indexes of insulin sensitivity were observed. Improvements in HOMA_IR and HOMA2‐%B were only related to the decrease in IHCL (r = 0.62, P < 0.01; r = 0.65, P = 0.002) and decreases in IHCL only correlated with the decrease in VAT (r = 0.61, P = 0.004). In conclusion, cross‐sectionally PAT is correlated with VAT, liver fat, and insulin resistance. Longitudinally, the association between PAT and insulin resistance was lost suggesting no causal relationship between the two.     

Routine Clinical Measures of Adiposity as Predictors of Visceral Fat in Adolescence: A Population-Based Magnetic Resonance Imaging Study

Objective

Visceral fat (VF) increases cardiometabolic risk more than fat stored subcutaneously. Here, we investigated how well routine clinical measures of adiposity, namely body mass index (BMI) and waist circumference (waist), predict VF and subcutaneous fat (SF) in a large population-based sample of adolescents. As body-fat distribution differs between males and females, we performed these analyses separately in each sex.

Design and Methods

VF and SF were measured by magnetic resonance imaging in 1,002 adolescents (482 males, age 12–18 years). Relationships of BMI and waist with VF and SF were tested in multivariable analyses, which adjusted for potentially confounding effects of age and height.

Results

In both males and females, BMI and waist were highly correlated with VF and SF, and explained 55–76% of their total variance. When VF was adjusted for SF, however, BMI and waist explained, respectively, only 0% and 4% of VF variance in males, and 4% and 11% of VF variance in females. In contrast, when SF was adjusted for VF, BMI and waist explained, respectively, 36% and 21% of SF variance in males, and 48% and 23% of SF variance in females. These relationships were similar during early and late puberty.

Conclusions and Relevance

During adolescence, routine clinical measures of adiposity predict well SF but not VF. This holds for both sexes and throughout puberty. Further longitudinal studies are required to assess how well these measures predict changes of VF and SF over time. Given the clinical importance of VF, development of cost-effective imaging techniques and/or robust biomarkers of VF accumulation that would be suitable in everyday clinical practice is warranted.     

Loss of Total and Visceral Adipose Tissue Mass Predicts Decreases in Oxidative Stress After Weight‐loss Surgery

It is not known whether there are mechanisms linking adipose tissue mass and increased oxidative stress in obesity. This study investigated associations between decreasing general and abdominal fat depots and oxidative stress during weight loss. Subjects were severely obese women who were measured serially at baseline and at 1, 6 (n = 30), and 24 months (n = 18) after bariatric surgery. Total fat mass (FAT) and volumes of visceral (VAT) and subcutaneous abdominal adipose tissue (SAT) were related to plasma concentrations of derivatives of reactive oxidative metabolites (dROMS), a measure of lipid peroxides and oxidative stress. After intervention, BMI significantly decreased, from 47.7 ± 0.8 kg/m² to 43.3 ± 0.8 kg/m² (1 month), 35.2 ± 0.8 kg/m² (6 months), and 30.2 ± 1.2 kg/m² (24 months). Plasma dROMS also significantly deceased over time. At baseline, VAT (r = 0.46), FAT (r = 0.42), and BMI (r = 0.37) correlated with 6‐month decreases in dROMS. Similarly, at 1 month, VAT (r = 0.43) and FAT (r = 0.41) correlated with 6‐month decreases in dROMS. Multiple regression analysis showed that relationships between VAT and dROMS were significant after adjusting for FAT mass. Increased plasma dROMS at baseline were correlated with decreased concentrations of high‐density lipoprotein (HDL) at 1 and 6 months after surgery (r = ?0.38 and ?0.42). This study found longitudinal associations between general, and more specifically intra‐abdominal adiposity, and systemic lipid peroxides, suggesting that adipose tissue mass contributes to oxidative stress.     

Familial Resemblance of 7‐Year Changes in Body Mass and Adiposity

Objective: To investigate the familial resemblance of 7‐year changes in body mass and adiposity among Canadian families. Research Methods and Procedures: The sample consisted of 655 women and 660 men from 521 families who participated in the Canada Fitness Survey in 1981 and the follow‐up Campbell's Survey in 1988. Indicators of baseline and 7‐year changes in body mass and adiposity included body mass (kilograms), body mass index (BMI; kilograms per square meter), sum of five skinfolds (SF5; millimeters), and waist circumference (WC; millimeters). The data were adjusted for the effects of age and sex, and the change scores were adjusted for baseline levels. A familial correlation model was used to determine the heritability of each phenotype using maximum likelihood techniques. Results: Significant familial resemblance was observed at baseline and for 7‐year changes in all phenotypes. At baseline, moderate heritabilities were observed [body mass: heritability coefficient (h²) = 56%; BMI, h² = 39%; SF5, h² = 41%; and WC, h² = 39%], whereas values were attenuated for each change score except for WC (Δbody mass, h² = 23%; ΔBMI, h² = 14%; ΔSF5, h² = 12%; and ΔWC, h² = 45%). Discussion: Changes in body mass and adiposity significantly aggregate within families over 7 years. However, baseline values are characterized by higher heritability levels except WC. The significant heritabilities observed for change scores suggest that lifestyle, transient environmental factors, and possibly age‐related gene effects are important determinants of changes in body mass and adiposity.     

Assessing Body Composition among 3‐ to 8‐Year‐Old Children: Anthropometry,BIA, and DXA

Objective: To examine the inter‐relationships of body composition variables derived from simple anthropometry [BMI and skinfolds (SFs)], bioelectrical impedance analysis (BIA), and dual energy x‐ray (DXA) in young children. Research Methods and Procedures: Seventy‐five children (41 girls, 34 boys) 3 to 8 years of age were assessed for body composition by the following methods: BMI, SF thickness, BIA, and DXA. DXA served as the criterion measure. Predicted percentage body fat (%BF), fat‐free mass (FFM; kilograms), and fat mass (FM; kilograms) were derived from SF equations [Slaughter (SL)1 and SL2, Deurenberg (D) and Dezenberg] and BIA. Indices of truncal fatness were also determined from anthropometry. Results: Repeated measures ANOVA showed significant differences among the methods for %BF, FFM, and FM. All methods, except the D equation (p = 0.08), significantly underestimated measured %BF (p < 0.05). In general, correlations between the BMI and estimated %BF were moderate (r = 0.61 to 0.75). Estimated %BF from the SL2 also showed a high correlation with DXA %BF (r = 0.82). In contrast, estimated %BF derived from SFs showed a low correlation with estimated %BF derived from BIA (r = 0.38); likewise, the correlation between DXA %BF and BIA %BF was low (r = 0.30). Correlations among indicators of truncal fatness ranged from 0.43 to 0.98. Discussion: The results suggest that BIA has limited utility in estimating body composition, whereas BMI and SFs seem to be more useful in estimating body composition during the adiposity rebound. However, all methods significantly underestimated body fatness as determined by DXA, and, overall, the various methods and prediction equations are not interchangeable.     

Loss of mitochondrial protease ClpP protects mice from diet‐induced obesity and insulin resistance

Caseinolytic peptidase P (ClpP) is a mammalian quality control protease that is proposed to play an important role in the initiation of the mitochondrial unfolded protein response (UPR^mt), a retrograde signaling response that helps to maintain mitochondrial protein homeostasis. Mitochondrial dysfunction is associated with the development of metabolic disorders, and to understand the effect of a defective UPR^mt on metabolism, ClpP knockout (ClpP^?/?) mice were analyzed. ClpP^?/? mice fed ad libitum have reduced adiposity and paradoxically improved insulin sensitivity. Absence of ClpP increased whole‐body energy expenditure and markers of mitochondrial biogenesis are selectively up‐regulated in the white adipose tissue (WAT) of ClpP^?/? mice. When challenged with a metabolic stress such as high‐fat diet, despite similar caloric intake, ClpP^?/? mice are protected from diet‐induced obesity, glucose intolerance, insulin resistance, and hepatic steatosis. Our results show that absence of ClpP triggers compensatory responses in mice and suggest that ClpP might be dispensable for mammalian UPR^mt initiation. Thus, we made an unexpected finding that deficiency of ClpP in mice is metabolically beneficial.     

CD38 deficiency suppresses adipogenesis and lipogenesis in adipose tissues through activating Sirt1/PPARγ signaling pathway

It has been recently reported that CD38 was highly expressed in adipose tissues from obese people and CD38‐deficient mice were resistant to high‐fat diet (HFD)‐induced obesity. However, the role of CD38 in the regulation of adipogenesis and lipogenesis is unknown. In this study, to explore the roles of CD38 in adipogenesis and lipogenesis in vivo and in vitro, obesity models were generated with male CD38^?/? and WT mice fed with HFD. The adipocyte differentiations were induced with MEFs from WT and CD38^?/? mice, 3T3‐L1 and C3H10T1/2 cells in vitro. The lipid accumulations and the alternations of CD38 and the genes involved in adipogenesis and lipogenesis were determined with the adipose tissues from the HFD‐fed mice or the MEFs, 3T3‐L1 and C3H10T1/2 cells during induction of adipocyte differentiation. The results showed that CD38^?/? male mice were significantly resistant to HFD‐induced obesity. CD38 expressions in adipocytes were significantly increased in WT mice fed with HFD, and the similar results were obtained from WT MEFs, 3T3‐L1 and C3H10T1/2 during induction of adipocyte differentiation. The expressions of PPARγ, AP2 and C/EBPα were markedly attenuated in adipocytes from HFD‐fed CD38^?/? mice and CD38^?/? MEFs at late stage of adipocyte differentiation. Moreover, the expressions of SREBP1 and FASN were also significantly decreased in CD38^?/? MEFs. Finally, the CD38 deficiency‐mediated activations of Sirt1 signalling were up‐regulated or down‐regulated by resveratrol and nicotinamide, respectively. These results suggest that CD38 deficiency impairs adipogenesis and lipogenesis through activating Sirt1/PPARγ‐FASN signalling pathway during the development of obesity.