Fat Partitioning Research Articles

Differential partitioning of coconut whey proteins and fat using aqueous two phase extraction

Production of Virgin Coconut Oil generates huge volumes of whey, a rich source of proteins, which is currently discarded as effluent or at best underutilized. Recovery of these proteins is a value addition improving the overall economics of the process. Aqueous two phase extraction was employed to recover these proteins from coconut whey. Besides the selection of phase forming salt and polymer molecular weight, the effect of various parameters such as tie line length (%TLL), volume ratio and pH was studied. Polyethylene glycol 6000/potassium phosphate system (5%/12% w/w, 0.2 vol ratio and 8.0 pH) was observed to be the most suitable system resulting in a recovery of 92.65% (w/w) in the salt-rich phase. Differential partitioning of protein and fat to the opposite phases (examined by phase contrast microscopy) was achieved at these conditions which facilitated the recovery of protein devoid of fat. A mechanism for the differential partitioning of whey proteins and oils is also proposed.

Substrate utilization and metabolic profile in response to overfeeding with a high-fat diet in South Asian and white men: a sedentary lifestyle study.

For the same BMI, South Asians have a higher body fat percentage, a higher liver fat content and a more adverse metabolic profile than whites. South Asians may have a lower fat oxidation than whites, which could result in an unfavorable metabolic profile when exposed to increased high-fat foods consumption and decreased physical activity as in current modern lifestyle. To determine substrate partitioning, liver fat accumulation and metabolic profile in South Asian and white men in response to overfeeding with high-fat diet under sedentary conditions in a respiration chamber. Ten South Asian men (BMI, 18-29 kg/m2) and 10 white men (BMI, 22-33 kg/m2), matched for body fat percentage, aged 20-40 year were included. A weight maintenance diet (30% fat, 55% carbohydrate, and 15% protein) was given for 3 days. Thereafter, a baseline measurement of liver fat content (1H-MRS) and blood parameters was performed. Subsequently, subjects were overfed (150% energy requirement) with a high-fat diet (60% fat, 25% carbohydrate, and 15% protein) over 3 consecutive days while staying in a respiration chamber mimicking a sedentary lifestyle. Energy expenditure and substrate use were measured for 3 × 24-h. Liver fat and blood parameters were measured again after the subjects left the chamber. The 24-h fat oxidation as a percentage of total energy expenditure did not differ between ethnicities (P = 0.30). Overfeeding increased liver fat content (P = 0.02), but the increase did not differ between ethnicities (P = 0.64). In South Asians, overfeeding tended to increase LDL-cholesterol (P = 0.08), tended to decrease glucose clearance (P = 0.06) and tended to elevate insulin response (P = 0.07) slightly more than whites. Despite a similar substrate partitioning and similar accretion of liver fat, overfeeding with high-fat under sedentary conditions tended to have more adverse effects on the lipid profile and insulin sensitivity in South Asians.

OR25-3 Toward a Circulating Marker of Hepato-Visceral Fat Excess: S100A4 in Adolescent Girls with Polycystic Ovary Syndrome

S100A4 has recently been identified as an adipokine that can serve as a marker of "pernicious" subcutaneous adipose tissue (Arner et al, Int J Ob 2018). However, S100A4 can also be released by an inflammatory subset of macrophages in the liver (Osterreicher et al, Proc Natl Acad Sci USA 2011). Development of polycystic ovary syndrome (PCOS) in adolescent girls is often driven by an early excess of fat in subcutaneous adipose tissue, accompanied by an excess of fat in ectopic locations, notably in viscera and liver (Cree-Green et al, Obesity 2016; de Zegher et al, Trends Endocrinol Metab 2018). Adolescent PCOS phenotypes are normalized more by preferential reduction of hepato-visceral adiposity with a low-dose combination of spironolactone, pioglitazone and metformin (SPIOMET) than by treatment with an oral contraceptive (OC) (Ibanez et al, J Adolesc Health 2017). Nowadays, the assessment of hepato-visceral adiposity (by magnetic resonance imaging) is rather cumbersome. In an attempt to identify a circulating marker of hepato-visceral fat excess, we studied whether S100A4 concentrations are elevated in adolescent girls with PCOS and, if so, whether they tend to normalize with OC or SPIOMET treatment. In 12 healthy controls and in 51 adolescent girls with PCOS (by International Consortium Update criteria; Ibanez et al, Horm Res Pediatr 2017), we assessed circulating S100A4 along with endocrine markers (including fasting insulin, SHBG, testosterone [by LC-MS/MS], high-molecular-weight adiponectin), body composition (by dual X-ray absorptiometry), and abdominal fat partitioning (by magnetic resonance imaging). Girls with PCOS were randomized for treatment with an OC (n=27) or SPIOMET (n=24) for 1 year, and the changes in their study endpoints were analysed. S100A4 concentrations were on average 71% (or 2.1 Z-score) higher in girls with PCOS than in controls (P<0.001), and they associated with hepato-visceral adiposity (r=0.47; p=0.001). Treatment with OC failed to lower the elevated S100A4 concentrations, whereas treatment with SPIOMET lowered circulating S100A4 toward normal (P<0.001 for within-group changes, and P<0.01 for between-group changes); on-treatment reduction of circulating S100A4 associated closely with reduction of hepato-visceral adiposity (r=0.50; p<0.0001). If the present findings are corroborated in other study cohorts with PCOS, then S100A4 is a first candidate-member of a future set of circulating markers that may simplify the diagnosis and follow-up of patients with PCOS, and perhaps also of patients with other phenotypes of central obesity.

Association Between Early Life Weight Gain and Abdominal Fat Partitioning at 4.5Years is Sex, Ethnicity, and Age Dependent.

The aim of this study was to investigate the independent associations between age-specific annual weight gain from birth to age 4years and fat deposition in metabolically distinct compartments at age 4.5years in a South Asian longitudinal birth cohort. Volumetric abdominal magnetic resonance imaging with comprehensive segmentation of deep and superficial subcutaneous adipose tissue (SAT) and visceral adipose tissues (VAT) was performed in 316 children (150 boys and 166 girls in three ethnic groups; 158 Chinese, 94 Malay, and 64 Indian) aged 4.5years. Associations between fat volumes and annual relative weight gain conditional on past growth were assessed overall and stratified by sex and ethnicity. Conditional relative weight gain had stronger associations with greater SAT and VAT at age 4.5years in girls than boys and in Indians compared with Malay and Chinese. Overall, the magnitude of association was the largest during 2 to 3years for SAT and 1 to 2years for VAT. Despite similar body weight, Indian children and girls had the highest deep and superficial SAT volumes at age 4.5years (all interactions P<0.05). No significant sex or ethnic differences were observed in VAT. With increasing BMI, Indian children had the highest tendency to accumulate VAT, and girls accumulated more fat than boys in all depots (all interactions P<0.001). Indian ethnicity and female sex predisposed children to accumulate more fat in the VAT depot with increasing conditional relative weight gain in the second year of life. Thus, 1 to 2years of age may be a critical window for interventions to reduce visceral fat accumulation.

Towards a circulating marker of hepato-visceral fat excess: S100A4 in adolescent girls with polycystic ovary syndrome - Evidence from randomized clinical trials.

S100A4 is a marker of subcutaneous adipose tissue dysfunction. Polycystic ovary syndrome (PCOS) is often driven by hepato-visceral adiposity. PCOS phenotypes are normalized more by reduction of central fat with spironolactone/pioglitazone/metformin (SPIOMET) than by oral contraceptive (OC) treatment. We studied whether circulating S100A4 concentrations are high in adolescents with PCOS and, if so, whether they normalize more with OC or SPIOMET. Assessments included circulating S100A4, endocrine markers, body composition, abdominal fat partitioning in controls (n=12) and girls with PCOS (n=51; age 15.8y; body mass index [BMI] 24.5kg/m2 ), and 1-year changes in girls with PCOS randomized for OC (n=27) or SPIOMET (n=24) treatment. Mean S100A4 concentrations were 71% higher (P<0.001) in girls with PCOS than in controls and associated with hepato-visceral adiposity (r=0.47; P=0.001); S100A4 concentrations decreased more (P<0.01) with SPIOMET, those decreases associating to hepato-visceral fat loss (r=0.50; P<0.0001). S100A4 may become a circulating marker of hepato-visceral fat excess in adolescents with PCOS.

The Impact of Weight Gain During HIV Treatment on Risk of Pre-diabetes, Diabetes Mellitus, Cardiovascular Disease, and Mortality.

Since the introduction of combined antiretroviral therapy (cART) and more effective treatments for AIDS, there has been a dramatic shift from the weight loss and wasting that characterised HIV/AIDS (and still does in countries where cART is not readily available or is initiated late) to healthy weight, or even overweight and obesity at rates mirroring those seen in the general population. These trends are attributable to several factors, including the “return to health” weight gain with reversal of the catabolic effects of HIV-infection following cART-initiation, strategies for earlier cART-initiation in the course of HIV-infection which have prevented many people living with HIV-infection from developing wasting, in addition to exposure to the modern obesogenic environment. Older cART regimens were associated with increased risk of body fat partitioning disorders (lipodystrophy) and cardiometabolic complications including atherothrombotic cardiovascular disease (CVD) and diabetes mellitus. Whilst cART now avoids those medications implicated in causing lipodystrophy, long-term cardiometabolic data on more modern cART regimens are lacking. Longitudinal studies show increased rates of incident CVD and diabetes mellitus with weight gain in treated HIV-infection. Abdominal fat gain, weight gain, and rising body mass index (BMI) in the short-term during HIV treatment was found to increase incident diabetes risk. Rising BMI was associated with increased risk of incident CVD, however the relationship varied depending on pre-cART BMI category. In contrast, a protective association with mortality is evident, predominantly in the underweight and in resource-poor settings, where weight gain reflects access to cART and virological suppression. The question of how to best evaluate, manage (and perhaps constrain) weight gain during HIV treatment is of clinical relevance, especially in the current climate of increasingly widespread cART use, rising overweight, and obesity prevalence and growing metabolic and cardiovascular disease burden in people living with HIV-infection. Large prospective studies to further characterise the relationship between weight gain during HIV treatment and risk of diabetes, CVD and mortality are required.

Benchmarks of Diabetes Care in Men Living With Treated HIV-Infection: A Tertiary Center Experience.

Treated human immunodeficiency virus (HIV) infection is associated with high rates of type 2 diabetes mellitus (DM), metabolic syndrome and central obesity/body fat partitioning disorders. To our knowledge, there are no available data comparing diabetes care in people with both HIV+DM vs. DM alone (DM-controls) within the same service and evaluating if benchmarked standards of care are being met in people with HIV+DM. This study evaluated the frequency that people with HIV+DM met the benchmarked American Diabetes Association (ADA) standards of care in diabetes (targets for HbA1c, blood pressure, lipid levels, complication screening, and healthy weight), compared to age- and sex- matched controls with diabetes, in an urban teaching hospital. The frequency of diabetes complications and rates of obesity and metabolic syndrome were also examined. All participants were male; individuals with HIV+DM (n = 30) were similar to DM-controls (n = 30) for age, diabetes duration and smoking status, but were more frequently non-obese compared to DM controls (92 vs. 55%, respectively, p = 0.003). Only 41% of HIV+DM met HbA1c targets, compared with 70% of DM-controls (p = 0.037). Blood pressure targets were poorly met in both HIV+DM and DM-controls: 43 vs. 23%, respectively (p = 0.12); LDL cholesterol targets were met in 65 vs. 67% (p = 1.0). Benchmarked complication screening rates were similar between HIV+DM vs. DM-controls for annual foot examination (53 vs. 67%, respectively, p = 0.29); biennial retinal examination (83 vs. 77%, respectively, p = 0.52); and annual urinary albumin measurement (77 vs. 67%, respectively, p = 0.39). The prevalence of diabetes complications was similar between HIV+DM compared to DM-controls: macrovascular complications were present in 23% in both groups (p = 1.0); the prevalence of microvascular complications was 40 vs. 30%, respectively (p = 0.51). Achieving the standard of care benchmarks for diabetes in people with both HIV-infection and diabetes is of particular importance to mitigate against the accelerated cardiometabolic outcomes observed in those with treated HIV infection. HIV+DM were less likely to achieve HbA1c targets than people with diabetes, but without HIV. People with HIV+DM may require specific strategies to ensure care benchmarks are met.

The sequence of prenatal growth restraint and postnatal catch-up growth: normal heart but thicker intima-media and more pre-peritoneal fat in late infancy.

The sequence of prenatal growth restraint and postnatal catch-up growth leads to a thicker intima-media and more pre-peritoneal fat by age 3-6years. To study whether carotid intima-media thickness (cIMT) and pre-peritoneal fat differ already between catch-up small-for-gestational-age (SGA) infants and appropriate-for-gestational-age (AGA) controls in late infancy (ages 1 and 2years) and whether such differences - if any - are accompanied by differences in cardiac morphology and function. Longitudinal assessments included body height and weight; fasting glucose, insulin, Insulin-like growth factor (IGF-I), high-molecular-weight adiponectin; body composition (by absorptiometry); cIMT, aortic IMT, pre-peritoneal fat partitioning (by ultrasound); cardiac morphometry and function (by echocardiography) in AGA and SGA infants at birth, at age 1year (N=87), and again at age 2years (N=68). Catch-up SGA infants had already a thicker cIMT than AGA controls at ages 1 and 2years, and more pre-peritoneal fat by age 2years (all p values between <0.01 and <0.0001); all cardiac and endocrine-metabolic results were similar in AGA and SGA infants at ages 1 and 2years. From late infancy onwards, catch-up SGA infants have a thicker cIMT and more pre-peritoneal fat than AGA controls, but their cardiac morphology and function remain reassuringly similar.

Ethnic differences in fat and muscle mass and their implication for interpretation of bioelectrical impedance vector analysis

According to the World Health Organization Expert Consultation, current body mass index (BMI) cut-offs should be retained as an international classification. However, there are ethnic differences in BMI-associated health risks that may be caused by differences in body fat or skeletal muscle mass and these may affect the interpretation of phase angle and bioelectrical impedance vector analysis (BIVA). Therefore, the aim of this study was to compare body composition measured by bioelectrical impedance analysis among 1048 German, 1026 Mexican, and 995 Japanese adults encompassing a wide range of ages and BMIs (18-78 years; BMI, 13.9-44.3 kg/m2). Regression analyses between body composition parameters and BMI were used to predict ethnic-specific reference values at the standard BMI cut-offs of 18.5, 25, and 30 kg/m2. German men and women had a higher fat-free mass per fat mass compared with Mexicans. Normal-weight Japanese were similar to Mexicans but approached the German phenotype with increasing BMI. The skeletal muscle index (SMI, kg/m2) was highest in Germans, whereas in BIVA, the Mexican group had the longest vector, and the Japanese group had the lowest phase angle and the highest extracellular/total body water ratio. Ethnic differences in regional partitioning of fat and muscle mass at the trunk and the extremities contribute to differences in BIVA and phase angle. In conclusion, not only the relationship between BMI and adiposity is ethnic specific; in addition, fat distribution, SMI, and muscle mass distribution vary at the same BMI. These results emphasize the need for ethnic-specific normal values in the diagnosis of obesity and sarcopenia.

Differences in relationships of maternal and paternal age at childbirth with body fat distribution in offspring.

Although delayed parenthood has been linked to various adverse health outcomes in offspring, little attention has been given to the relationship between an increased parental age at childbirth and fat distribution in offspring. We aimed to determine the relationship between parental age at childbirth and body fat partitioning in Chinese children. A total of 463 children (mean age, 8 years; 43% female) were recruited. Dual-energy X-ray absorptiometry was used to determine the fat mass (FM) and percentage of fat mass (%FM) in various areas of the body. Weight and height were measured. The body mass index (BMI) and fat mass index (FMI) were calculated. A questionnaire was used to collect information about parental variables and other confounders. Multiple linear regression analyses suggested that for each additional year of maternal age at delivery, the BMI, FMI, and FM at whole-body, trunk, android, gynoid, and appendicular region increased by 0.115 kg/m2 , 0.076 kg/m2 ; 128.4 g, 57.71 g, 10.96 g, 25.07 g, and 67.88 g, respectively, after adjusting for covariates (P = .002-.017). In the analysis of covariance, children of mothers aged ≥31 years exhibited higher BMI, FMI, total-body and segmental FM, compared to those of mothers aged ≤25 years (P-trend = 0.002-0.017). Similar tendencies were also observed for the %FM (P-trend = 0.002-0.017). However, there was no significant relationship between paternal age at childbirth and any of the body fat measures in children. An increasing maternal age at childbirth was associated with increased body fat accumulation in offspring, whereas paternal age at childbirth appeared to have no such association.

Aberrant fatty acid metabolism in skeletal muscle contributes to insulin resistance in zinc transporter 7 (znt7)-knockout mice

ZnT7 (Slc30a7) is a widely expressed zinc transporter involved in sequestration of zinc into the Golgi apparatus and vesicular compartments. znt7-knockout (KO) mice are mildly zinc-deficient and lean. Despite their lean phenotype, adult male znt7-KO mice are prone to insulin resistance. We hypothesized that fat partitioning from adipose to nonadipose tissues causes insulin resistance in znt7-KO mice. Here, we used biological and biochemical methods, including fatty acid and oxylipin profiling, EM, immunohistochemistry, quantitative RT-PCR, and Western blot analysis, to identify the underlying mechanism of insulin resistance in znt7-KO mice. We found that insulin resistance in this model was primarily associated with increased intracellular fatty acid levels in the skeletal muscle, which promoted intracellular lipid accumulation and production of bioactive lipid mediators, such as 12,13-dihydroxyoctadecanoic acid (12,13-DiHOME) and 12-hydroxyeicosatetraenoic acid (12-HETE). The expression of fatty acid-binding protein 3 (Fabp3) was dramatically up-regulated in the znt7-KO muscle cells accompanied by increased expression of Cd36, Slc27a1, and Slc27a4, the three major fatty acid transporters in the skeletal muscle. We also demonstrated that znt7-KO muscle cells had increased fatty acid oxidative capacity, indicated by enlarged mitochondria and increased mRNA or protein expression of key enzymes involved in the fatty acid mitochondrial shuttle and β-oxidation. We conclude that increased fatty acid uptake in the znt7-KO skeletal muscle is a key factor that contributes to the excessive intracellular lipid deposit and elevated production of bioactive lipid mediators. These mediators may play pivotal roles in oxidative stress and inflammation, leading to insulin resistance.

The “adipose tissue expandability” hypothesis: a potential mechanism for insulin resistance in obese youth

Obesity has become a major global health challenge of the 21st century, as it is associated with the onset of type 2 diabetes (T2D) and cardiovascular complications, even at a very early age in life. The root causes of pediatric obesity remain incompletely understood. The obesity epidemic together with the relationship of obesity to the growing population burden of chronic disease presents unprecedented research opportunities and challenges. Decades of obesity-related research funded by governments around the world have yielded many important discoveries about both etiological pathways and preventive or therapeutic interventions. Yet, there is a sense that the problem is outpacing these research efforts. Obesity poses a significant risk for the development of cardiovascular disease (CVD) , diabetes and certain cancers thereby shortening life expectancy. Nevertheless, many obese individuals do not develop any of these comorbidities. One hypothesis explaining this dilemma is that total body fat is not the culprit of adverse health in obesity rather the relative proportion of lipids in various fat depots is what determines the metabolic risk. In this review, we describe the role of altered fat partitioning in youth onset obesity and its relation to fatty liver and T2D during adolescence.

Liver volume and hepatic adiposity in childhood: relations to body growth and visceral fat.

The sequence of prenatal growth restraint and postnatal catch-up growth may lead to hepato-visceral adiposity, insulin resistance and low-grade inflammation before the onset of puberty. In prepubertal children born appropriate for gestational age (AGA) or small for gestational age (SGA), we assessed potential relationships between the aforementioned sequence and liver volume. The study population consisted of 86 children (41 AGA and 45 SGA with catch-up growth; age (mean±s.e.m.), 8.5±0.1 years), recruited into two prospective longitudinal studies. Anthropometry, endocrine-metabolic variables and inflammatory and hepatic markers were assessed, along with liver volume, hepatic adiposity and abdominal fat partitioning (by magnetic resonance imaging). AGA and SGA children differed in hepato-visceral adiposity, but had similar liver volumes. Boys had larger livers than girls, and higher sex hormone binding globulin and inflammation markers. Liver volume correlated with height Z-score, body mass index Z-score, HOMA-IR (homeostasis model assessment-insulin resistance) and with subcutaneous and visceral fat, but not with birth weight Z-score or with hepatic adiposity. Height, visceral fat, gender and HOMA-IR were major determinants of liver volume, together explaining 61% of its variance. The trajectory from prenatal restraint, via postnatal catch-up, to hepato-visceral adiposity and insulin resistance does not appear to be detectably influenced by prepubertal alterations of liver volume. Further follow-up will disclose the potential role of liver volume in the pubertal segment of this trajectory, and whether the augmented fat content and visceral adiposity in SGA subjects is followed by the development of metabolic syndrome and hepatic dysfunction in adulthood.

Role of Gut Microbiota and Short Chain Fatty Acids in Modulating Energy Harvest and Fat Partitioning in Youth.

We aimed at determining the relationship of the gut microbiota and short chain fatty acids with obesity and fat partitioning and at testing potential differences in the ability of gut microbiota to ferment equal amounts of carbohydrates (CHO) between lean and obese youth. We analyzed the gut microbiota of 84 youth in whom body fat distribution was measured by fast-magnetic resonance imaging, de novo lipogenesis (DNL) quantitated using deuterated water, and the capability of gut flora to ferment CHO was assessed by 13C-fructose treatment in vitro. A significant association was found between the Firmicutes to Bacteroidetes ratio, and the abundance of Bacteroidetes and Actinobacteria with body mass index, visceral and SC fat (all P < .05). Plasma acetate, propionate, and butyrate were associated with body mass index and visceral and SC fat (all P < .05) and with hepatic DNL (P = .01, P = .09, P = .04, respectively). Moreover, the rate of CHO fermentation from the gut flora was higher in obese than in lean subjects (P = .018). These data demonstrate that obese youth show a different gut flora composition than lean and that short chain fatty acids are associated with body fat partitioning and DNL. Also, the gut microbiota of obese youth have a higher capability than the gut flora of lean to oxidize CHO.

Endothelial Function in Youth: A Biomarker Modulated by Adiposity-Related Insulin Resistance

To investigate the physical and metabolic determinants of endothelial dysfunction, an early marker of subclinical atherosclerosis, in normal weight and overweight adolescents with and without type 2 diabetes mellitus. A cross-sectional study of 81 adolescents: 21 normal weight, 25 overweight with normal glucose tolerance, 19 overweight with impaired glucose regulation, and 16 with type 2 diabetes mellitus underwent evaluation of reactive hyperemia index (RHI) and augmentation index (AIx) at heart rate 75 bpm by peripheral arterial tonometry; oral glucose tolerance test, lipid profile, and hyperinsulinemic-euglycemic clamp to measure insulin sensitivity; and dual energy X-ray absorptiometry scan and abdominal magnetic resonance imaging for percentage of body fat and abdominal fat partitioning. Participants across tertiles of RHI (1.2 ± 0.02, 1.5 ± 0.02, and 2.0 ± 0.05, P < .001) had similar age, sex, race, lipid profile, and blood pressure. Body mass index z-score, percentage body fat, abdominal fat, and hemoglobin A1c decreased, and insulin sensitivity increased from the first to third tertile. RHI was inversely related to percentage body fat (r = -0.29, P = .008), total (r = -0.37, P = .004), subcutaneous (r = -0.39, P = .003), and visceral (r = -0.26, P = .04) abdominal fat. AIx at heart rate 75 bpm was higher (worse) in the lower RHI tertiles (P = .04), was positively related to percentage body fat (r = 0.26, P = .021), and inversely related to age, insulin sensitivity, and inflammatory markers (tumor necrosis factor-α and plasminogen activator inhibition-1). Childhood obesity, particularly abdominal adiposity, is associated with endothelial dysfunction manifested by worse reactive hyperemia and higher AIx. Insulin resistance appears to mediate this relationship.

A Role of the Inflammasome in the Low Storage Capacity of the Abdominal Subcutaneous Adipose Tissue in Obese Adolescents.

The innate immune cell sensor leucine-rich–containing family, pyrin domain containing 3 (NLRP3) inflammasome controls the activation of caspase-1, and the release of proinflammatory cytokines interleukin (IL)-1β and IL-18. The NLRP3 inflammasome is implicated in adipose tissue inflammation and the pathogenesis of insulin resistance. Herein, we tested the hypothesis that adipose tissue inflammation and NLRP3 inflammasome are linked to the downregulation of subcutaneous adipose tissue (SAT) adipogenesis/lipogenesis in obese adolescents with altered abdominal fat partitioning. We performed abdominal SAT biopsies on 58 obese adolescents and grouped them by MRI-derived visceral fat to visceral adipose tissue (VAT) plus SAT (VAT/VAT+SAT) ratio (cutoff 0.11). Adolescents with a high VAT/VAT+SAT ratio showed higher SAT macrophage infiltration and higher expression of the NLRP3 inflammasome–related genes (i.e., TLR4, NLRP3, IL1B, and CASP1). The increase in inflammation markers was paralleled by a decrease in genes related to insulin sensitivity (ADIPOQ, GLUT4, PPARG2, and SIRT1) and lipogenesis (SREBP1c, ACC, LPL, and FASN). Furthermore, SAT ceramide concentrations correlated with the expression of CASP1 and IL1B. Infiltration of macrophages and upregulation of the NLRP3 inflammasome together with the associated high ceramide content in the plasma and SAT of obese adolescents with a high VAT/VAT+SAT may contribute to the limited expansion of the subcutaneous abdominal adipose depot and the development of insulin resistance.

Sleep efficiency as a determinant of insulin sensitivity in overweight and obese adolescents.

Insulin resistance (IR) occurs in a transient manner during puberty. Obese adolescents may be at risk for persistent IR during puberty. The objective of the study is to review the literature on the association of the anthropometry and lifestyle characteristics with insulin sensitivity in overweight and obese adolescents, and include data from a new study. Relevant papers were selected and reviewed. In addition, 137 overweight and obese adolescents (42 male/95 female, age 14.4 ± 2.3 years, BMI z-score +3.3 ± 0.7, HOMA-IR 3.4 ± 1.8) from the Centre for Overweight Adolescent and Children's Healthcare (MUMC+) were included in this study. Anthropometrics, Tanner stages, sleep characteristics, food intake behaviour and physical activity were determined, and possible associations with homeostasis model assessment of insulin resistance (HOMA-IR) were tested. Overweight and obese adolescents with unfavourable fat partitioning and family history of NIDDM are at risk for persistent IR. Overweight and obese adolescents from the new cohort showed a higher HOMA-IR postpubertally. BMI z-score, age, pubertal stage and prepubertally total sleeping time (TST) and sleep efficiency (SE) were identified as significant contributors. Overweight and obese adolescents showed a persistently higher instead of transiently higher HOMA-IR during puberty, associated with BMI z-score, age, pubertal stage and prepubertally less TST and SE.

Ethnic Differences in the Role of Adipocytokines Linking Abdominal Adiposity and Insulin Sensitivity Among Asians.

Among Asian ethnic groups, Chinese or Malays are more insulin sensitive than South Asians, in particular in lean individuals. We have further reported that body fat partitioning did not explain this ethnic difference in insulin sensitivity. We examined whether adipocytokines might explain the ethnic differences in the relationship between obesity and insulin resistance among the three major ethnic groups in Singapore. This was a cross-sectional study of 101 Chinese, 82 Malays, and 81 South Asian men. Insulin sensitivity index (ISI) was measured using hyperinsulinemic euglycemic clamp. Visceral (VAT) and subcutaneous adipose tissue (SAT) volumes were quantified using magnetic resonance imaging. Plasma total and high-molecular-weight adiponectin, leptin, visfatin, apelin, IL-6, fibroblast growth factor 21 (FGF21), retinol binding protein-4 (RBP 4), and resistin were measured using enzyme-linked immunoassays. Principle component (PC) analysis on the adipocytokines identified three PCs, which explained 49.5% of the total variance. Adiponectin loaded negatively, and leptin and FGF21 loaded positively onto PC1. Visfatin, resistin, and apelin all loaded positively onto PC2. IL-6 loaded positively and RBP-4 negatively onto PC3. Only PC1 was negatively associated with ISI in all ethnic groups. In the path analysis, SAT and VAT were negatively associated with ISI in Chinese and Malays without significant mediatory role of PC1. In South Asians, the relationship between VAT and ISI was mediated partly through PC1, whereas the relationship between SAT and ISI was mediated mainly through PC1. The relationships between abdominal obesity, adipocytokines and insulin sensitivity differ between ethnic groups. Adiponectin, leptin, and FGF21 play a mediating role in the relationship between abdominal adiposity and insulin resistance in South Asians, but not in Malays or Chinese.

The sequence of prenatal growth restraint and post-natal catch-up growth leads to a thicker intima-media and more pre-peritoneal and hepatic fat by age 3-6 years.

Infants born small-for-gestational-age (SGA) who develop post-natal weight catch-up are at risk for insulin resistance, central adiposity and cardiovascular disease in later life, even in the absence of overweight. In young (age 3-6 years) non-obese SGA children, we assessed arterial health (as judged by intima-media thickness [IMT]) and abdominal fat distribution (subcutaneous, visceral, preperitoneal and hepatic components by magnetic resonance imaging [MRI] and/or ultrasound [US]) besides a selection of endocrine markers. Comparisons of measures in SGA (n = 27) vs. appropriate-for-GA (AGA) children (n = 19) of similar height, weight and body mass index. Longitudinal outcomes (age 3-6 years) were carotid IMT (cIMT); fasting glucose, circulating insulin, IGF-I and high-molecular-weight (HMW) adiponectin; abdominal fat partitioning by US. Cross-sectional outcomes (age 6 years) were aortic IMT (aIMT) and abdominal fat partitioning by MRI. At 3 and 6 years, cIMT and IGF-I results were higher and HMW adiponectin lower in SGA than AGA children; at 6 years, SGA subjects had also a thicker aIMT and more pre-peritoneal and hepatic fat, and were less insulin sensitive (all P values between <0.05 and <0.0001). cIMT correlated positively with pre-peritoneal fat, particularly at 6 years. Post-SGA status and weight gain in early childhood (between 3 and 6 years) were independent predictors of cIMT at 6 years, explaining 48 % of its variance. SGA children aged 3-6 years were found to have a thicker intima- media and more pre-peritoneal and hepatic fat than AGA children of comparable size.

Visceral adiposity is negatively associated with bone density and muscle attenuation

The storage of adipose tissue in ectopic compartments is a hallmark attribute linking greater body mass index (BMI) with cardiometabolic diseases. Despite ample evidence to confirm that increased visceral adipose tissue (VAT) deposition occurs with obesity, the interrelations between altered fat partitioning and regional muscle and bone quality are less well understood. We examined the association between adiposity and spinal muscle and bone quality across a large, heterogeneous cohort of adults. We identified 8833 thoracic or abdominal computed tomography scans from patients in the University of Michigan Health System who were aged 18-64.9 y. We measured trabecular bone densities, cortical bone densities, VAT areas, and subcutaneous adipose tissue (SAT) areas at vertebral levels T7 to L5. Psoas muscle attenuation (an indicator of fat infiltration in muscle) was measured at the L4 level. Muscle attenuation as well as trabecular and cortical bone densities revealed negative correlations with BMI, SAT, and VAT. The correlation between BMI and psoas attenuation was -0.321, between BMI and the density of cortical bone was -0.250, and between BMI and trabecular bone was -0.143 (all P < 0.001). However, correlations between VAT and lower muscle attenuation were stronger as were those between VAT and lower bone densities. Inverse correlations between VAT and densities of psoas muscle and cortical and trabecular bone were -0.460, -0.407, and -0.434, respectively (P < 0.001). Even after adjustment for age, sex, and BMI, partial correlations between VAT, muscle attenuation, and bone densities remained significant at -0.250, -0.119, and -0.216, respectively (P < 0.001). Contrary to previous reports that high body mass is associated with increased bone quality, our data show a significant negative association between BMI and muscle and bone densities, suggesting fat infiltration into these tissues. More importantly, correlations between VAT and decreased bone and muscle densities remained statistically significant even after adjustment for age, sex, and BMI.