Suresh Anand Sadananthan

Automated segmentation of visceral and subcutaneous (deep and superficial) adipose tissues in normal and overweight men.

To develop an automatic segmentation algorithm to classify abdominal adipose tissues into visceral fat (VAT), deep (DSAT), and superficial (SSAT) subcutaneous fat compartments and evaluate its performance against manual segmentation.

Faster eating rates are associated with higher energy intakes during an ad libitum meal, higher BMI and greater adiposity among 4-5 year-old children: results from the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) cohort

Faster eating rates are associated with increased energy intake, but little is known about the relationship between childrens eating rate, food intake and adiposity. We examined whether children who eat faster consume more energy and whether this is associated with higher weight status and adiposity. We hypothesised that eating rate mediates the relationship between child weight and ad libitum energy intake. Children (n 386) from the Growing Up in Singapore Towards Healthy Outcomes cohort participated in a video-recorded ad libitum lunch at 4·5 years to measure acute energy intake. Videos were coded for three eating-behaviours (bites, chews and swallows) to derive a measure of eating rate (g/min). BMI and anthropometric indices of adiposity were measured. A subset of children underwent MRI scanning (n 153) to measure abdominal subcutaneous and visceral adiposity. Children above/below the median eating rate were categorised as slower and faster eaters, and compared across body composition measures. There was a strong positive relationship between eating rate and energy intake (r 0·61, P<0·001) and a positive linear relationship between eating rate and childrens BMI status. Faster eaters consumed 75 % more energy content than slower eating children (Δ548 kJ (Δ131 kcal); 95 % CI 107·6, 154·4, P<0·001), and had higher whole-body (P<0·05) and subcutaneous abdominal adiposity (Δ118·3 cc; 95 % CI 24·0, 212·7, P=0·014). Mediation analysis showed that eating rate mediates the link between child weight and energy intake during a meal (b 13·59; 95 % CI 7·48, 21·83). Children who ate faster had higher energy intake, and this was associated with increased BMI z-score and adiposity.

Skeletal muscle lipid metabolism studied by advanced magnetic resonance spectroscopy.

0079-6565/

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

see front matter 2012 Elsevier B.V. A doi:10.1016/j.pnmrs.2012.02.002 Abbreviations: ATP, adenosine tri-phosphate; BMI chemical shift selective; CSI, chemical shift imaging; D planar imaging; EPSI, echo-planar spectroscopic imagi lateralis; GM, gastrocnemius medialis; IMCL, intra-m constant time correlation spectroscopy; MRI, magnet number of averages; NMR, nuclear magnetic resonan fatty acids; RDC, residual dipolar coupling; RF, radio fr lateral; STEAM, stimulated echo mode; SVS, single vox pulses with optimized relaxation delays; WET, water ⇑ Corresponding author at: Laboratory of Molecu 64788757; fax: +65 64788732. E-mail address: Sendhil_Velan@sbic-a-star.edu.sg 2012 Elsevier B.V. All rights reserved.

Differentiating Brown and White Adipose Tissues by High-Resolution Diffusion NMR Spectroscopy

CONTEXT 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. OBJECTIVE 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. DESIGN AND PARTICIPANTS 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. MAIN OUTCOME MEASURES 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. RESULTS 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. CONCLUSIONS 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.

Effect of Exercise and Calorie Restriction on Tissue Acylcarnitines, Tissue Desaturase Indices, and Fat Accumulation in Diet-Induced Obese Rats

There are two types of fat tissues, white adipose tissue (WAT) and brown adipose tissue (BAT), which essentially perform opposite functions in whole body energy metabolism. There is a large interest in identifying novel biophysical properties of WAT and BAT by a quantitative and easy-to-run technique. In this work, we used high-resolution pulsed field gradient diffusion NMR spectroscopy to study the apparent diffusion coefficient (ADC) of fat molecules in rat BAT and WAT samples. The ADC of fat in BAT and WAT from rats fed with a chow diet was compared with that of rats fed with a high-fat diet to monitor how the diffusion properties change due to obesity-associated parameters such as lipid droplet size, fatty acid chain length, and saturation. Feeding a high-fat diet resulted in increased saturation, increased chain lengths, and reduced ADC of fat in WAT. The ADC of fat was lower in BAT relative to WAT in rats fed both chow and high-fat diets. Diffusion of fat was restricted in BAT due to the presence of small multilocular lipid droplets. Our findings indicate that in vivo diffusion might be a potential way for better delineation of BAT and WAT in both lean and obese states.

Regulation of glucose metabolism in non-diabetic, metabolically-obese normal-weight Asians

Both exercise and calorie restriction interventions have been recommended for inducing weight-loss in obese states. However, there is conflicting evidence on their relative benefits for metabolic health and insulin sensitivity. This study seeks to evaluate the differential effects of the two interventions on fat mobilization, fat metabolism, and insulin sensitivity in diet-induced obese animal models. After 4 months of ad libitum high fat diet feeding, 35 male Fischer F344 rats were grouped (n = 7 per cohort) into sedentary control (CON), exercise once a day (EX1), exercise twice a day (EX2), 15% calorie restriction (CR1) and 30% calorie restriction (CR2) cohorts. Interventions were carried out over a 4-week period. We found elevated hepatic and muscle long chain acylcarnitines with both exercise and calorie restriction, and a positive association between hepatic long chain acylcarnitines and insulin sensitivity in the pooled cohort. Our result suggests that long chain acylcarnitines may not indicate incomplete fat oxidation in weight loss interventions. Calorie restriction was found to be more effective than exercise in reducing body weight. Exercise, on the other hand, was more effective in reducing adipose depots and muscle triglycerides, favorably altering muscle/liver desaturase activity and improving insulin sensitivity.

Moderate Weight Loss Improves Body Composition and Metabolic Function in Metabolically Unhealthy Lean Subjects: Weight Loss in MONW Subjects

Type 2 diabetes in Asia occurs largely in the absence of obesity. The metabolically obese normal-weight (MONW) phenotype refers to lean subjects with metabolic dysfunction that is typically observed in people with obesity and is associated with increased risk for diabetes. Previous studies evaluated MONW subjects who had greater body mass index (BMI) or total body fat than respective control groups, making interpretation of the results difficult. We evaluated insulin sensitivity (hyperinsulinemic-euglycemic clamp); insulin secretion (mixed meal with oral minimal modeling); intra-abdominal, muscle, and liver fat contents (magnetic resonance); and fasting and postprandial glucose and insulin concentrations in 18 MONW subjects and 18 metabolically healthy controls matched for age (43 ± 3 and 40 ± 3 yr; P = 0.52), BMI (both 22 ± 1 kg/m2; P = 0.69), total body fat (17 ± 1 and 16 ± 1 kg; P = 0.33), and sex (9 men and 9 women in each group). Compared with controls, MONW subjects had an approximately twofold greater visceral adipose tissue volume and an approximately fourfold greater intrahepatic fat content (but similar muscle fat), 20-30% lower glucose disposal rates and insulin sensitivity, and 30-40% greater insulin secretion rates (all P < 0.05). The disposition index, fasting glucose, and HbA1c concentrations were not different between groups, whereas postprandial glucose and insulin concentrations were ~15% and ~65% greater, respectively, in MONW than control subjects (both P < 0.05). We conclude that the MONW phenotype is associated with accumulation of fat in the intra-abdominal area and the liver, profound insulin resistance, but also a robust β-cell insulin secretion response that compensates for insulin resistance and helps maintain glucose homeostasis.

Sex differences in glucose and fatty acid metabolism in non-obese Asians.

Individuals who have “metabolically obese normal weight” (MONW) have an increased risk for cardiometabolic disease. Moderate weight loss has multiple benefits in people with obesity, but its effects in lean people are unknown. Thus, the effects of diet‐induced 5% weight loss on body composition and metabolic function in MONW subjects were evaluated.

Low Dose Levothyroxine Reduces Intrahepatic Lipid Content in Patients with Type 2 Diabetes Mellitus and NAFLD.

Context The prevalence of diabetes is increasing throughout Asia, even in the absence of obesity, and is lower in women than in men. The underlying mechanisms are not well understood. Objective To evaluate the sex differences in glucose and fatty acid metabolism in Asians who are nonobese. Design Cross-sectional study. Setting Clinical Nutrition Research Centre, Singapore. Participants Healthy Asian men (n = 32; body mass index, 21.8 ± 1.5 kg/m2; age, 42 ± 14 years) and women (n = 28; body mass index, 21.4 ± 2.0 kg/m2; age, 41 ± 13 years). Main Outcome Measures Insulin sensitivity (insulin-mediated glucose uptake normalized for steady-state insulin; hyperinsulinemic-euglycemic clamp), postprandial glucose, insulin and fatty acid concentrations, insulin secretion (mixed meal tolerance test with mathematical modeling), insulin clearance, body composition and fat distribution (dual-energy X-ray absorptiometry, MRI, and spectroscopy), cardiorespiratory fitness (maximal oxygen uptake; graded exercise test), and handgrip strength (dynamometry). Results Women had more total body fat but less visceral fat than men; liver and muscle lipid contents were not different. Maximal oxygen uptake and handgrip strength were lower in women than men. The postprandial glucose concentrations were ~8% lower, the insulin-mediated glucose uptake was ~16% greater, and the meal-induced suppression of fatty acid concentrations was significantly greater in women than in men (P < 0.05 for all). However, muscle insulin sensitivity was not different between the sexes. No differences were found in postprandial insulin secretion and clearance rates; however, the steady-state insulin clearance was ~17% lower in women. Conclusions Asian women who are nonobese are more insulin-sensitive than men at the level of adipose tissue but not skeletal muscle. Therefore, sex differences in glucose tolerance are likely the result of sexual dimorphism in hepatic insulin action.