Hepatic triglyceride content and its relation to body adiposity: a magnetic resonance imaging and proton magnetic resonance spectroscopy study

BACKGROUND: Hepatic steatosis is associated with obesity and type II diabetes. Proton magnetic resonance spectroscopy (1H MRS) is a non-invasive method for measurement of tissue fat content, including intrahepatocellular lipids (IHCL) and intramyocellular lipids (IMCL). PATIENTS AND METHODS: We used 1H MRS and whole body magnetic resonance imaging (MRI) to assess the relationship between IHCL accumulation, total body adipose tissue (AT) content/distribution, and IMCL content in 11 subjects with biopsy proven hepatic steatosis and 23 normal volunteers. RESULTS: IHCL signals were detectable in all subjects but were significantly greater in hepatic steatosis (geometric mean (GM) 11.5 (interquartile range (IQR) 7.0-39.0)) than in normal volunteers (GM 2.7 (IQR 0.7-9.3); p=0.02). In the study group as a whole, IHCL levels were significantly greater in overweight compared with lean subjects (body mass index (BMI) >25 kg/m2 (n=23): GM 7.7 (IQR 4.0-28.6) v BMI <25 kg/m2 (n=11): GM 1.3 (IQR 0.3-3.6; p=0.004)). There was a significant association between IHCL content and indices of overall obesity (expressed as a percentage of body weight) for total body fat (p=0.001), total subcutaneous AT (p=0.007), and central obesity (subcutaneous abdominal AT (p=0.001) and intra-abdominal AT (p=0.001)), after allowing for sex and age. No correlation between IHCL content and IMCL was observed. A significant correlation was observed between serum alanine aminotransferase and liver fat content (r=0.57, p=0.006). CONCLUSIONS: Our results suggest that hepatic steatosis appears to be closely related to body adiposity, especially central obesity. MRS may be a useful method for monitoring IHCL in future interventional studies.     

Pioglitazone added to conventional lipid-lowering treatment in familial combined hyperlipidaemia improves parameters of metabolic control: relation to liver, muscle and regional body fat content

Familial combined hyperlipidaemia (FCHL) is a complex genetic disorder conferring high risk of premature atherosclerosis, characterized by high cholesterol and/or triglyceride, low high density lipoprotein (HDL) cholesterol and insulin resistance. We examined whether pioglitazone, added to conventional lipid-lowering therapy, would favourably affect metabolic parameters and alter body fat content. We undertook a randomized, double blind, placebo-controlled study in 22 male patients with FCHL treated with pioglitazone or matching placebo 30 mg daily for 4 weeks, increasing to 45 mg for 12 weeks. Magnetic resonance imaging and proton magnetic resonance spectroscopy were performed to measure adipose tissue (AT) body content as well as intrahepatocellular lipids (IHCL) and intramyocellular lipids (IMCL) at baseline and after treatment. Significantly improved in the pioglitazone group were: triglyceride/HDL (atherogenic index of plasma) -32.3% (p=0.002), plasma glucose -4.4% (p=0.03), alanine-aminotransferase (ALT) -7.7% (p=0.005) and adiponectin 130.1% (p=0.001). Pioglitazone treatment resulted in a significant increase in total (5.3%, p=0.02) and subcutaneous (7.1%, p=0.003) adipose tissue as well as in soleus-IMCL levels (47.4%, p=0.02) without alteration in intra-abdominal AT or IHCL. Changes in ALT and AST and IHCL were strongly correlated (r=0.72, p<0.01; r=.0.86, p<0.01, respectively). In patients with FCHL on conventional lipid-lowering therapy, the addition of pioglitazone acts favourably on several metabolic parameters.     

Women and men have similar amounts of liver and intra-abdominal fat,despite more subcutaneous fat in women: implications for sex differences in markers of cardiovascular risk

Aims/hypothesis Fat accumulation in the liver has been shown to be closely correlated with hepatic insulin resistance and features of insulin resistance, also independently of body weight. It remains to be established how fat in the liver correlates with that in other depots, and whether any association differs between men and women.Methods Liver fat (assessed using proton spectroscopy), intra-abdominal and subcutaneous fat (measured using magnetic resonance imaging) and markers of insulin resistance, including serum adiponectin, were determined in 132 non-diabetic subjects: 66 men (age 41±1 years) and 66 women (age 42±1 years).Results Although the women had almost twice as much subcutaneous fat as the men (5045±207 vs 2610±144 cm³, p<0.0001), amounts of intra-abdominal fat (1305±80 vs 1552±111 cm³, NS) and liver fat (6.7±0.8 vs 8.9±1.2%, NS) were similar. In this study, no sex differences were observed with respect to serum insulin, adiponectin, triglyceride and HDL cholesterol concentrations. Of all measures of body composition, liver fat was best correlated with serum insulin (r=0.58, p<0.001), with no difference observed between men and women. Serum adiponectin was inversely correlated with liver fat content (r=–0.21, p<0.05). Multiple linear regression analysis revealed that intra-abdominal fat was significantly associated with liver fat, independently of serum adiponectin and subcutaneous fat. Liver fat, but not intra-abdominal fat, significantly explained the variation in serum insulin concentrations.Conclusions/interpretation Intra-abdominal fat is independently associated with liver fat, whereas subcutaneous fat is not. Liver fat, but not intra-abdominal fat, is independently associated with serum insulin. Men and women with similar amounts of intra-abdominal and liver fat do not exhibit sex differences in markers of insulin resistance (serum insulin, triglycerides, HDL cholesterol and adiponectin).Abbreviations ALT alanine aminotransferase - AST aspartate aminotransferase - GGT gamma glutamyl transferase - MRI magnetic resonance imaging - NAFLD non-alcoholic fatty liver disease - SNP single nucleotide polymorphism     

Body fat distribution and flow-mediated endothelium-dependent vasodilation in older men

OBJECTIVE: Recent studies indicate that abdominal fat accumulation, in particular intra-abdominal fat, is related to impaired endothelial function in young healthy volunteers. The aim of this study was to examine whether the distribution of body fat depots is related to impaired endothelial function in older men. METHODS: Cross-sectional sample of 38 older (68+/-1 y) sedentary (VO(2max)=2.4+/-0.1 l/min) men. Flow-mediated endothelial dependent vasodilation (EDD) was assessed in the brachial artery in response to reactive hyperemia using high-resolution ultrasound. Abdominal subcutaneous and visceral fat depots were assessed by computed tomography scan (CT-scan) at the L(4)-L(5) region in the supine position. Percentage body fat was assessed via dual-energy X-ray absorptiometry (DEXA). RESULTS: Flow-mediated percentage change in brachial artery was 7.6+/-0.7%, suggesting an impaired flow-mediated EDD. Using simple linear regression analysis, there were no statistically significant relationship observed between flow-mediated EDD and the indices of total and abdominal adiposity (percentage body fat=29.3+/-0.9%, r=-0.11; total abdominal fat area=465+/-23 cm(2), r=-0.1; intra-abdominal fat area=200+/-14 cm(2), r=-0.14; subcutaneous fat area=265+/-13 cm(2), r=-0.05; BMI=29.3+/-0.9 kg/m(2), r=-0.07; and waist to hip ratio=0.98+/-0.01, r=-0.20). CONCLUSION: These findings suggest that in older sedentary men there is no clear correlation between adiposity and body fat distribution and impairment of flow-mediated endothelium dependent vasodilation.     

The role of intramyocellular lipids during hypoglycemia in patients with intensively treated type 1 diabetes

CONTEXT: Endocrine defensive mechanisms provide for energy supply during hypoglycemia. Intramyocellular lipids (IMCL) were recently shown to contribute to energy supply during exercise. OBJECTIVE: The objective of this study was to assess the contribution of IMCL compared with lipolysis and endogenous glucose production (EGP) to insulin-mediated hypoglycemia counterregulation in patients with type 1 diabetes mellitus (T1DM). DESIGN AND SETTING: This was a prospective explorative study performed in a university research facility. PARTICIPANTS: Six well-controlled T1DM (age, 29 +/- 4 yr; body mass index, 23.4 +/- 1.0 kg/m2; hemoglobin A1c, 6.3 +/- 0.1%) and six nondiabetic humans (controls; age, 28 +/- 2 yr; body mass index, 23.4 +/- 1.0 kg/m2; hemoglobin A1c, 5.1 +/- 0.1%) were studied. INTERVENTIONS: We performed 240-min hypoglycemic (approximately 3 mM)-hyperinsulinemic (0.8 mU/kg x min) clamps on separate days to measure: 1) systemic lipolysis ([2H5]glycerol turnover), EGP ([6,6-(2)H2]glucose), and local lipolysis in abdominal s.c. adipose tissue and gastrocnemius muscle (microdialysis); and 2) IMCL (by 1H nuclear magnetic resonance spectroscopy) in soleus and tibialis anterior muscle. MAIN OUTCOME MEASURES: The main outcome measures were changes in IMCL during prolonged hypoglycemia. RESULTS: At baseline, EGP, glycerol turnover, and IMCL were not different between the groups. During hypoglycemia, hormonal counterregulation was blunted in T1DM (peak: glucagon, 68 +/- 4 vs. 170 +/- 37 pg/ml; cortisol, 16 +/- 2 vs. 24 +/- 2 microg/dl; epinephrine, 274 +/- 84 vs. 597 +/- 212 pg/ml; all P < 0.05 vs. control). T1DM had approximately 50% lower EGP (4.6 +/- 0.6 vs. 10.9 +/- 0.5 micromol/kg x min; P < 0.005), but approximately 40% higher glycerol turnover (374 +/- 21 vs. 272 +/- 19 micromol/kg x min; P < 0.01). Glycerol concentrations in muscle (T1DM, 302 +/- 22 control, 346 +/- 17 micromol/liter) and adipose tissue (264 +/- 25 vs. 318 +/- 25 micromol/liter) did not differ between groups. IMCL in soleus and tibialis anterior muscle did not change from baseline during hypoglycemia. CONCLUSIONS: In well-controlled T1DM, impaired hypoglycemia counterregulation is associated with decreased glucose production and augmented whole body lipolysis, which cannot be explained by either hydrolysis of muscle triglycerides or increased abdominal s.c. adipose tissue lipolysis.     

Weight loss and body fat distribution: a feasibility study using computed tomography.

Computerized tomography (CT) was used to assess the effect of a loss of body weight (18.8 kg) on the size of five fat depots in 11 obese postmenopausal women: the abdominal subcutaneous and visceral depots, the pelvic subcutaneous and intrapelvic depots, and the thigh subcutaneous depot. The mean decrease in total body fat was 34 percent, with comparable decreases in total abdominal fat (33 percent) and total pelvic fat (32 percent). In the abdomen, visceral fat was reduced by 35 percent and subcutaneous fat by 33 percent. In the pelvic region, intrapelvic fat decreased by 51 percent and subcutaneous fat by 25 percent. The decrease in the size of the abdominal visceral fat depot was highly correlated with fat loss during treatment (r = 0.68). By contrast, the decrease in the size of the subcutaneous abdominal fat depot correlated less highly with fat loss. These preliminary findings suggest that obese postmenopausal women with large visceral fat depots will decrease the size of their visceral fat depots by weight reduction. This is good news since the adverse health effects of obesity are believed to be associated with visceral fat.     

The effect of a single 2 h bout of aerobic exercise on ectopic lipids in skeletal muscle,liver and the myocardium

Aims/hypothesis

Ectopic lipids are fuel stores in non-adipose tissues (skeletal muscle [intramyocellular lipids; IMCL], liver [intrahepatocellular lipids; IHCL] and heart [intracardiomyocellular lipids; ICCL]). IMCL can be depleted by physical activity. Preliminary data suggest that aerobic exercise increases IHCL. Data on exercise-induced changes on ICCL is scarce. Increased IMCL and IHCL have been related to insulin resistance in skeletal muscles and liver, whereas this has not been documented in the heart. The aim of this study was to assess the acute effect of aerobic exercise on the flexibility of IMCL, IHCL and ICCL in insulin-sensitive participants in relation to fat availability, insulin sensitivity and exercise capacity.

Methods

Healthy physically active men were included. $ \overset{\cdot }{V}{\mathrm{O}}_{2 \max } $ was assessed by spiroergometry and insulin sensitivity was calculated using the HOMA index. Visceral and subcutaneous fat were separately quantified by MRI. Following a standardised dietary fat load over 3 days, IMCL, IHCL and ICCL were measured using MR spectroscopy before and after a 2 h exercise session at 50–60% of $ \overset{\cdot }{V}{\mathrm{O}}_{2 \max } $ . Metabolites were measured during exercise.

Results

Ten men (age 28.9?±?6.4 years, mean ± SD; $ \overset{\cdot }{V}{\mathrm{O}}_{2 \max } $ 56.3?±?6.4 ml kg^?1 min^?1; BMI 22.75?±?1.4 kg/m²) were recruited. A 2 h exercise session resulted in a significant decrease in IMCL (?17?±?22%, p?=?0.008) and ICCL (?17?±?14%, p?=?0.002) and increase in IHCL (42?±?29%, p?=?0.004). No significant correlations were found between the relative changes in ectopic lipids, fat availability, insulin sensitivity, exercise capacity or changes of metabolites during exercise.

Conclusions/interpretation

In this group, physical exercise decreased ICCL and IMCL but increased IHCL. Fat availability, insulin sensitivity, exercise capacity and metabolites during exercise are not the only factors affecting ectopic lipids during exercise.     

Excess visceral and hepatic adipose tissue in Turner syndrome determined by magnetic resonance imaging: estrogen deficiency associated with hepatic adipose content

Obesity, predominantly centrally distributed, is common in women with Turner syndrome (TS) and is thought to contribute to the increased risk of atherosclerosis; however, insulin concentrations are unexpectedly low. To explore this discrepancy, we assessed fat content and distribution by magnetic resonance imaging (MRI) and bioelectrical impedance (BI). Six nondiabetic, estrogen-treated women with TS were compared with six age-matched normal controls of similar body mass index. Clinical history, anthropometric measurements, biochemical markers, and MRI and BI measures of adiposity were assessed. TS women had increased intrahepatocellular lipids (IHCL) on MRI. After height adjustment, they also had an excess of total and visceral compared with sc adipose tissue (AT) than controls, without elevated insulin concentrations. BI and MRI measures correlated strongly for total and sc, but not visceral, AT in TS. IHCL was associated with cumulative estrogen-deficient years (r = 0.928; P = 0.008). Women with TS depart from the classical picture of metabolic syndrome despite an excess of total and visceral AT on MRI. Elevated IHCL in TS is associated with estrogen deficiency. BI may be useful to estimate total body fat, but does not reliably localize fat depots in TS.     

Improvement of glucose and lipid metabolism associated with selective reduction of intra-abdominal visceral fat in premenopausal women with visceral fat obesity.

Visceral fat obesity (VFO) with predominant intra-abdominal fat accumulation has been shown to be more often associated with metabolic disorders than subcutaneous fat obesity (SFO). In the present study, changes in fat distribution and their effects on metabolic complications were investigated in forty premenopausal female obese patients in whom substantial weight reduction was obtained by means of a low calorie diet. Analysis of fat distribution by CT scanning demonstrated that visceral fat decreased to a greater extent than abdominal subcutaneous fat, which was particularly evident in VFO patients. On the other hand, change of fat distribution was small in SFO patients. That is, visceral to subcutaneous abdominal fat ratio (V/S ratio) decreased from 0.62 +/- 0.36 to 0.46 +/- 0.33 in VFO, whereas from 0.23 +/- 0.07 to 0.20 +/- 0.09 in SFO after weight reduction. Although obese patients, especially those with VFO, were frequently associated with glucose intolerance and hyperlipidemia, marked diminution was observed in the elevated levels of plasma glucose area on 75g OGTT, serum total cholesterol and triglyceride after weight reduction. By the examination of interrelationship between the changes in body weight, BMI, total and regional fat volume and changes in glucose and lipid metabolism, we found that the decrease in the V/S ratio and visceral fat volume were more strongly correlated with the improvement in plasma glucose and lipid metabolism compared to the decrease in body weight, BMI, total fat volume and abdominal subcutaneous fat volume. Furthermore, partial correlation analyses demonstrated that the metabolic improvements were associated with changes in visceral abdominal fat after control for changes in total adipose tissue volume.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of menopausal status on body composition and abdominal fat distribution

OBJECTIVE: Preliminary studies suggest that the menopause transition is associated with deleterious changes in body composition and abdominal fat distribution. Limitations of the methodology used in these studies, however, render their conclusions controversial. Thus, the present study used radiologic imaging techniques to examine the effect of menopausal status on body composition and abdominal fat distribution. DESIGN: Cross-sectional. SUBJECTS: Fifty-three healthy, middle-aged, premenopausal women (mean+/-SD; 47+/-3 y) and 28 early-postmenopausal women (51+/-4 y). MEASUREMENTS: Total and regional body composition by dual energy X-ray absorptiometry and abdominal fat distribution by computed tomography. RESULTS: No differences in total body fat-free mass or appendicular skeletal muscle mass were noted between groups. In contrast, total body fat mass was 28% higher (23+/-7 vs 18+/-7 kg) and percentage fat 17% higher (35+/-6 vs 30+/-9%; both P<0.01) in postmenopausal women compared with premenopausal women. Postmenopausal women had a 49% greater intra-abdominal (88+/-32 vs 59+/-32 cm2; P<0.01) and a 22% greater abdominal subcutaneous fat area (277+/-93 vs 227+/-108 cm2; P<0.05) compared to premenopausal women. The menopause-related difference in intra-abdominal fat persisted (P<0.05) after statistical adjustment for age and total body fat mass, whereas no difference in abdominal subcutaneous fat was noted. A similar pattern of differences in total and abdominal adiposity was noted in sub-samples of pre- and postmenopausal women matched for age or fat mass. CONCLUSION: Our data suggest that early-postmenopausal status is associated with a preferential increase in intra-abdominal fat that is independent of age and total body fat mass. International Journal of Obesity (2000) 24, 226-231     

Sex differences in regional distribution of fat cell size and lipoprotein lipase activity in morbidly obese patients

Adipose tissue distribution is an important predictor of obesity-associated morbidity and mortality. A central ('male') fat distribution is associated with increases in intra-abdominal adipose tissue which might be of metabolic importance. Although many recent studies have pointed out significant regional differences in the size and metabolism of subcutaneous fat cells intra-abdominal depots have not been systematically examined. We compared fat cell sizes (FCS) and lipoprotein lipase activity (LPLA) of two internal (omental, mesenteric) and four subcutaneous (SQ) sites (femoral, gluteal, abdominal, epigastric) in morbidly obese patients (26 premenopausal women and 14 men). Men had larger internal FCS than women while women had larger SQ FCS in the gluteal and femoral depots. Mesenteric FCS were largest of all sites in men. In women, omental fat cells were the smallest of all sites sampled but omental fat cells were as large as SQ sites in men. A more central distribution of fat in women (high waist/hip ratio) was associated with large mesenteric fat cells. Calculation of total fat cell number based on SQ FCS only, revealed sex differences that were eliminated by also using intra-abdominal FCS in the calculation. Averaged across all six sites, women had higher LPLA than men. Higher LPL activities were found in the lower-body subcutaneous sites with enlarged fat cells in women. However, the relative enlargement of intra-abdominal FCS in men was not associated with increased LPLA. In conclusion, sex- and site-specific variations in the distribution of FCS and LPLA in internal and SQ fat depots emphasize the importance of analyzing these depots in studies of fat cell number and adipose tissue metabolism.     

Body fat distribution and cardiovascular risk in normal weight women. Associations with insulin resistance, lipids and plasma leptin

OBJECTIVE: To systematically examine the correlations between insulin resistance, plasma leptin concentration, obesity and the distribution of fat assessed by anthropometry and magnetic resonance imaging in Asian women. DESIGN: A cross sectional study of non-diabetic, normal weight women. SUBJECTS: Twenty-one healthy women aged 38.8 y (s.d. 11.7) and BMI 22.6 kg/m2 (s.d. 2.3). MEASUREMENTS: Intraperitoneal, retroperitoneal and subcutaneous abdominal fat volume was assessed by magnetic resonance imaging. Anthropometric data were collected. Total fat mass was assessed by bioelectric impedance analysis. Fasting serum lipids, insulin and plasma leptin were assayed. RESULTS: Generalized obesity correlated with subcutaneous abdominal fat mass (r=0.83, P<0.001), but not with intra-abdominal fat mass. Both intraperitoneal fat mass and retroperitoneal fat mass increased with age (r=0.58, P=0.005 and r=0. 612, P=0.003, respectively). Abdominal subcutaneous fat mass was the most important determinant of insulin resistance and plasma leptin. Of the serum lipids, only fasting triglyceride correlated significantly with the waist-to-hip ratio. CONCLUSIONS: It is possible that the large size of the subcutaneous depot compared to the intra-abdominal depot overwhelms any metabolic differences between adipose tissue from these two sites, resulting in the stronger correlation between insulin resistance and subcutaneous abdominal fat mass rather than intra-abdominal fat mass. On the other hand, the distribution of fat between subcutaneous fat depots may be important in the metabolic syndrome given the correlation of fasting triglyceride with waist to hip ratio but not with abdominal fat. However, the study population was small, younger and leaner compared to previous studies and we may not be able to generalize these results to all segments of the population. We confirm that subcutaneous fat mass is the major determinant of plasma leptin.     

The -913 G/A glutamine:fructose-6-phosphate aminotransferase gene polymorphism is associated with measures of obesity and intramyocellular lipid content in nondiabetic subjects

Increases in glutamine:fructose-6-phosphate aminotransferase (GFAT) protein levels directly activate flux through the hexosamine biosynthetic pathway. This pathway has been involved as a fuel sensor in energy metabolism and development of insulin resistance. We screened the 5'-flanking region of the human GFAT gene for polymorphisms and subsequently genotyped 412 nondiabetic, metabolically characterized Caucasians for the two single-nucleotide polymorphisms (SNP) at positions -913 (G/A) and -1412 (C/G) with rare allele frequencies of 42% and 16%, respectively. The -913 G SNP was associated with significantly higher body mass index and percent body fat in men (P = 0.02 and 0.004, respectively), but not in women (P = 0.47 and 0.26, respectively). In the subgroup of individuals (n = 193) who underwent hyperinsulinemic-euglycemic clamp, an association of the -913 G SNP with insulin sensitivity independent of body mass index was not detected. Moreover, the -913 G allele in a group of 71 individuals who had undergone magnetic resonance spectroscopy was associated with higher intramyocellular lipid content (IMCL) in tibialis anterior muscle (4.21 +/- 0.31 vs. 3.36 +/- 0.35; P = 0.04) independent of percent body fat and maximal aerobic power. The -1412 SNP had no effect on percent body fat, insulin sensitivity, or IMCL. In conclusion, we identified two polymorphisms in the 5'-flanking region of GFAT, of which the -913 SNP seems to alter the risk for obesity and IMCL accumulation in male subjects.     

Liver fat is not a marker of metabolic risk in lean premenopausal women

We examined the independent associations among abdominal adipose tissue (AT) depots, liver fat, cardiorespiratory fitness (CRF), and metabolic risk factors in 86 lean premenopausal women. We measured abdominal AT and liver fat by computed tomography (CT), and CRF by a maximal treadmill exercise test. Liver fat was not related to any abdominal AT depot, metabolic risk factor, or CRF (P > .10). Visceral AT mass (kilograms) remained a significant (P < .05) predictor of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), TC/high-density lipoprotein cholesterol (HDL-C), and LDL-C/HDL-C after statistical adjustment for CRF. Abdominal subcutaneous AT mass was also a significant (P < .05) correlate of TC/HDL-C and LDL-C/HDL-C after control for CRF. Visceral AT remained a significant predictor (P < .05) of TC and LDL-C after control for abdominal subcutaneous AT. Conversely, subcutaneous AT did not remain a significant correlate after control for visceral AT. However, the deep subcutaneous AT depot remained significantly associated with LDL-C, TC/HDL-C, and LDL-C/HDL-C after control for visceral AT. In contrast, visceral AT remained correlated with triglycerides (TG) alone, after control for the deep subcutaneous AT. These observations suggest that liver fat is not a determinant of metabolic risk in lean women. Conversely, both visceral and the deep subcutaneous depot are determinants of metabolic risk in premenopausal woman despite the absence of obesity.     

Sonography detection of small intra-abdominal fat variations.

The aim of this study was to check the reliability of sonography in measuring small variations in quantities of subcutaneous and intra-abdominal fat. Twenty-six obese women (BMI 39 +/- 6) underwent a 15 day very low calorie diet. The study included, both before and after very low calorie diet, computed tomography measurements of total (AT), visceral (VAT) and subcutaneous (SAT) adipose tissue areas, visceral/subcutaneous area ratio (V/S), waist/hip circumference ratio measurements (W/H), and ultrasound measurements of abdominal subcutaneous skin-muscle thickness, intra-abdominal muscle-aorta thickness and intra-abdominal/subcutaneous thickness ratio. Weight reduction was from 101 +/- 17 to 95 +/- 16 kg (P less than 0.001). W/H dropped from 0.83 +/- 0.06 to 0.82 +/- 0.07 (n.s.). VAT dropped from 158 +/- 72 to 134 +/- 61 cm2 (P less than 0.005), SAT from 572 +/- 151 to 566 +/- 164 cm2 (n.s.) and V/S from 0.29 +/- 0.15 to 0.25 +/- 0.11 (P less than 0.01). Abdominal subcutaneous fat thickness decreased from 36 +/- 8 to 35 +/- 10 mm (n.s.), intra-abdominal thickness from 39 +/- 25 to 20 +/- 20 mm (P less than 0.001) and intra-abdominal/subcutaneous from 1.1 +/- 0.7 to 0.8 +/- 0.6 (P less than 0.005). VAT measurement accurately identified small intra-abdominal fat variations. W/H could not evaluate visceral fat loss, because of simultaneous decreases in waist and hip circumferences. Ultrasound was able to measure small reductions in intra-abdominal fat.     

Is the reduction of lower-body subcutaneous adipose tissue associated with elevations in risk factors for diabetes and cardiovascular disease?

AIMS/HYPOTHESIS: Since the accumulation of lower-body subcutaneous adipose tissue (LBSAT) is associated with decreased cardiometabolic risk, we evaluated whether reductions in LBSAT independent of changes in visceral AT (VAT) and abdominal SAT are associated with elevations in diabetes and cardiovascular disease risk factors. METHODS: Overweight and obese men (n = 58) and premenopausal women (n = 49) with elevated cardiometabolic risk underwent 3 months of diet and/or exercise induced weight-loss treatment; regional body composition assessment by magnetic resonance imaging (MRI); and cardiometabolic risk assessment, including an OGTT. RESULTS: After control for potential confounders, reductions in VAT, abdominal SAT and LBSAT were all associated with improvements in selective cardiometabolic risk factors, including fasting glucose levels, lipid status and OGTT glucose and insulin. Independent of changes in the other AT depots, reductions in VAT and abdominal SAT, but not LBSAT, remained associated with improvement in fasting glucose levels, glucose tolerance and lipid status. CONCLUSIONS/INTERPRETATION: Among overweight and obese adults with increased cardiometabolic risk, the selective reduction of LBSAT is not associated with elevations in risk factors for diabetes and cardiovascular disease. Thus, the reduction of excess AT conveys health benefit regardless of origin.     

The effect of obesity on the ratio of type 3 17beta-hydroxysteroid dehydrogenase mRNA to cytochrome P450 aromatase mRNA in subcutaneous abdominal and intra-abdominal adipose tissue of women

OBJECTIVES: To investigate (1) whether type 3 17beta-hydroxysteroid dehydrogenase (17beta-HSD), the enzyme which catalyzes the conversion of androstenedione to testosterone in the testis, is co-expressed with P450aromatase in the preadipocytes of women, and (2) whether the relative expression of type 3 17beta-HSD and aromatase varies in subcutaneous abdominal vs intra-abdominal adipose tissue of women. SUBJECTS: Subcutaneous abdominal and intra-abdominal adipose tissue was obtained from women undergoing elective abdominal surgery (age 22-78 y, body mass index (BMI) 22.4-52.9 kg/m(2)). MEASUREMENTS: Expression of type 3 17beta-HSD in adipose cell fractions was determined using RT-PCR. Preadipocyte steroidogenesis was investigated in primary cultures using androstenedione as substrate. Messenger RNA levels for type 3 17beta-HSD and aromatase were measured in adipose tissue from the subcutaneous abdominal and intra-abdominal depots using a quantitative multiplex competitive RT-PCR assay. RESULTS: Type 3 17beta-HSD is co-expressed with aromatase in the abdominal preadipocytes of women. Cultured preadipocytes from both subcutaneous abdominal (n=5) and intra-abdominal (n=5) sites converted androstenedione to testosterone, and there was minimal conversion of androstenedione to estrone. Consistent with this, the levels of type 3 17beta-HSD mRNA were significantly higher than aromatase mRNA at both sites (P<0.05; n=8 subcutaneous abdominal, n=12 intra-abdominal adipose tissue). The ratio of levels of 17beta-HSD mRNA to aromatase mRNA in intra-abdominal adipose tissue was positively correlated with BMI (n=11, r=0.61, P<0.05) and waist circumference (n=10, r=0.65, P<0.05). The converse was found in subcutaneous abdominal adipose tissue. CONCLUSION: The intra-abdominal adipose tissue of women may be substantially androgenic, increasingly so with increasing obesity, particularly central obesity. While androgen production by this adipose tissue deposit may not contribute to circulating testosterone levels due to hepatic clearance, it may have hitherto unrecognised local effects in the intra-abdominal adipose tissue and also on the liver via the hepatic portal system. These studies suggest a mechanism linking central obesity with insulin resistance and dyslipidaemia.     

Assessment of abdominal fat development in young adolescents using magnetic resonance imaging

OBJECTIVE: To determine the patterns of change and the best anthropometric indicators of intra-abdominal fat deposition in young adolescents from ages 11-13 y. SUBJECTS: Subjects were 25 boys (mean age 13.7 +/- 0.32 y) and 17 girls (mean age of 13.7 +/- 0.23 y) who had taken part in a similar study 2 y earlier at ages 11.5 +/- 0.33 y and 11.5 +/- 0.27 y, respectively. METHODS: Intra-abdominal (IA) and subcutaneous adipose (SA) tissue areas and IA/SA ratio were determined through four tranverse magnetic resonance imaging scans on two occasions. Differences were investigated using t-tests and ANOVA. Skinfolds, girths and circumferences, body mass index and hydrostatic weighing were also recorded. Pearson correlation coefficients and regression equations were calculated to determine the best anthropometric indicators of intra-abdominal fat deposition. RESULTS: Intra-abdominal fat and subcutaneous fat areas had significantly increased in boys and girls by the second measure. Boys had deposited greater amounts of fat in intra-abdominal depots so that their intra-abdominal/subcutaneous ratio had increased significantly from 0.31 to 0.39. This had reduced in girls from 0.39 to 0.35. However, patterns of change were variable within sexes. Truncal skinfold sites (r = 0.54-0.70) emerged as the best field indicators of intra-abdominal fat deposition. CONCLUSIONS: Patterns of intra-abdominal and subcutaneous fat distribution are identifiable in pubescent children using magnetic resonance imaging. An acceptable indication is provided by truncal skinfolds.     

Contributions of total body fat, abdominal subcutaneous adipose tissue compartments, and visceral adipose tissue to the metabolic complications of obesity

Obesity is related to the risk for developing non-insulin-dependent diabetes mellitus (NIDDM), hypertension, and cardiovascular disease. Visceral adipose tissue (VAT) has been proposed to mediate these relationships. Abdominal subcutaneous adipose tissue (SAT) is divided into 2 layers by a fascia, the fascia superficialis. Little is known about the radiologic anatomy or metabolic correlates of these depots. The objective of this study was to relate the amounts of VAT, SAT, deep subcutaneous abdominal adipose tissue (DSAT), and superficial subcutaneous abdominal adipose tissue (SSAT) to gender and the metabolic complications of obesity after adjusting for total body fat and to discuss the implications of these findings on the measurement of adipose tissue mass and adipose tissue function. The design was a cross-sectional database study set in a nutrition research center. Subjects included 199 volunteers participating in nutrition research protocols who also had computed tomography (CT) and dual energy x-ray absorptiometry (DEXA) measurement of body fat. The amount of DSAT was sexually dimorphic, with women having 51% of the subcutaneous abdominal fat in the deep layer versus 66% for men (P <.05). Abdominal fat compartments were compared with metabolic variables before and after adjusting for body fat measured by DEXA using 2 separate methods. The unadjusted correlation coefficients between the body fat measures, R(2), were largest for fasting insulin and triglyceride and smaller for high-density lipoprotein (HDL) cholesterol and blood pressure. A large portion of the variance of fasting insulin levels in both men and women was explained by total body fat. In both men and women, the addition of VAT and subcutaneous abdominal adipose tissue depots only slightly increased the R(2). In men, when body fat compartments were considered independently, DSAT explained a greater portion of the variance (R(2) =.528) in fasting insulin than VAT (R(2) =.374) or non-VAT, non-DSAT subcutaneous adipose tissue (R(2) =.375). These data suggest that total body fat is a major contributor to the metabolic sequelae of obesity, with specific fat depots, VAT, and DSAT also making significant contributions.     

Serum resistin and hepatic fat content in nondiabetic individuals

CONTEXT: Serum resistin concentration is increased in patients with nonalcoholic fatty liver disease in proportion with the histological severity of the disease, but the relevance of the contribution of fatty liver per se is undetermined. OBJECTIVE: The objective of the study was to assess the relationship between serum resistin and the degree of ectopic fat accumulation in vivo in humans. DESIGN AND SETTING: The hepatic fat (IHF) content, measured quantitatively by means of 1H magnetic resonance spectroscopy, serum resistin, and biochemical and hormonal metabolic correlates of fatty liver and insulin resistance were assessed in 28 affected patients, and 47 individuals with comparable anthropometric features served as controls. Insulin sensitivity was estimated using the computer homeostatic model assessment (HOMA)-2. A subset of volunteers (n = 18) also underwent 1H magnetic resonance spectroscopy of the calf muscles to assess the intramyocellular lipid content (IMCL). RESULTS: In patients with fatty liver, the IHF content (13 +/- 8 vs. 2 +/- 1% wet weight; P < 0.0001) and also the soleus IMCL content (P < 0.05) were increased in comparison with the controls. Patients with fatty liver had lower insulin sensitivity (HOMA2 insulin sensitivity: 59 +/- 24 vs. 72 +/- 29%; P < 0.04), serum resistin (3.4 +/- 0.8 vs. 3.9 +/- 1.0 ng/ml; P < 0.02), and adiponectin (P < 0.01) concentrations. Serum resistin was inversely correlated with the IHF content (r = -0.35; P < 0.003) and the soleus IMCL content (r = -0.51; P < 0.05) but not HOMA2 insulin sensitivity. CONCLUSION: This study demonstrates that excessive ectopic fat accumulation in the liver and skeletal muscle of insulin-resistant subjects is associated with lower serum resistin concentration and not with hyperresistinemia.