Hyperleptinemia: an early sign of juvenile obesity. Relations to body fat depots and insulin concentrations

1996 ◽  
Vol 271 (3) ◽  
pp. E626-E630 ◽  
Author(s):  
S. Caprio ◽  
W. V. Tamborlane ◽  
D. Silver ◽  
C. Robinson ◽  
R. Leibel ◽  
...  
Keyword(s):  
Body Fat ◽  
Fat Mass ◽  
Visceral Fat ◽  
Subcutaneous Fat ◽  
Ventromedial Hypothalamus ◽  
Strong Positive Correlation ◽  
Fat Depots ◽  
Hyperglycemic Clamp ◽  
Juvenile Obesity ◽  
Fat Depot

Leptin, the OB gene product, is an adipocyte-derived circulating protein. In several rodent models of obesity, such as the db/db mice, fa/fa rats, and ventromedial hypothalamus-lesioned mice, as well as adult obese subjects, leptin mRNA expression and the circulating levels are elevated, suggesting resistance to its action. However, it is unknown whether the rise in leptin concentration occurs early in the natural evolution of human obesity or is a chronic adaptation to the obese state. Moreover, whether the distribution of body fat (i.e., visceral vs. subcutaneous abdominal fat) influences circulating leptin levels has not been assessed. We have determined in a group of obese and nonobese children and young adults whether leptin levels 1) are increased early in the development of obesity, 2) are related to a specific fat depot measured by magnetic resonance imaging, 3) vary during hyperinsulinemic, euglycemic, and hyperglycemic clamp studies, and 4) are different in males vs. females. In the basal state, leptin levels were elevated in obese children. Children and adults demonstrated a strong positive correlation between leptin concentrations and the subcutaneous fat depot (r = 0.84, P < 0.001). Surprisingly, a weaker correlation was found with visceral fat mass (r = 0.59, P = 0.001). Leptin levels remained unchanged under both euglycemic and hyperglycemic hyperinsulinemic conditions in both obese and nonobese subjects. A pronounced effect of gender on leptin levels was also observed. We conclude that, early in the development of juvenile obesity, leptin concentrations are elevated and are more closely linked to subcutaneous than visceral fat mass. Acute increases in insulin concentrations do not affect circulating leptin levels.

scholarly journals The key role of a glucagon-like peptide-1 receptor agonist in body fat redistribution

2019 ◽  
Vol 240 (2) ◽  
pp. 271-286 ◽  
Author(s):  
Li Zhao ◽  
Chunfang Zhu ◽  
Meng Lu ◽  
Chi Chen ◽  
Xiaomin Nie ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Body Fat ◽  
Visceral Fat ◽  
Subcutaneous Fat ◽  
Control Group ◽  
Acid Oxidation ◽  
High Dose ◽  
Fat Depots ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are an ideal therapy for type 2 diabetes and, as of recently, for obesity. In contrast to visceral fat, subcutaneous fat appears to be protective against metabolic diseases. Here, we aimed to explore whether liraglutide, a GLP-1RA, could redistribute body fat via regulating lipid metabolism in different fat depots. After being fed a high-fat diet for 8 weeks, 50 male Wistar and Goto-Kakizaki rats were randomly divided into a normal control group, a diabetic control group, low- and high-dose liraglutide-treated groups and a diet-control group. Different doses of liraglutide (400 μg/kg/day or 1200 μg/kg/day) or an equal volume of normal saline were administered to the rats subcutaneously once a day for 12 weeks. Body composition and body fat deposition were measured by dual-energy X-ray absorptiometry and MRI. Isotope tracers were infused to explore lipid metabolism in different fat depots. Quantitative real-time PCR and Western blot analyses were conducted to evaluate the expression of adipose-related genes. The results showed that liraglutide decreased visceral fat and relatively increased subcutaneous fat. Lipogenesis was reduced in visceral white adipose tissue (WAT) but was elevated in subcutaneous WAT. Lipolysis was also attenuated, and fatty acid oxidation was enhanced. The mRNA expression levels of adipose-related genes in different tissues displayed similar trends after liraglutide treatment. In addition, the expression of browning-related genes was upregulated in subcutaneous WAT. Taken together, the results suggested that liraglutide potentially redistributes body fat and promotes browning remodeling in subcutaneous WAT to improve metabolic disorders.

scholarly journals Advanced Molecular Imaging (MRI/MRS/1H NMR) for Metabolic Information in Young Adults with Health Risk Obesity

Life ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1035
Author(s):  
Khin Thandar Htun ◽  
Jie Pan ◽  
Duanghathai Pasanta ◽  
Montree Tungjai ◽  
Chatchanok Udomtanakunchai ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Young Adults ◽  
Molecular Imaging ◽  
Body Fat ◽  
Visceral Fat ◽  
Fat Distribution ◽  
Fat Depots ◽  
The Metabolic Syndrome ◽  
Fat Depot ◽  
The Impact

Background: Obesity or being overweight is a medical condition of abnormal body fat accumulation which is associated with a higher risk of developing metabolic syndrome. The distinct body fat depots on specific parts of the anatomy have unique metabolic properties and different types of regional excessive fat distribution can be a disease hazard. The aim of this study was to identify the metabolome and molecular imaging phenotypes among a young adult population. Methods: The amount and distribution of fat and lipid metabolites profile in the abdomen, liver, and calf muscles of 46 normal weight, 17 overweight, and 13 obese participants were acquired using MRI and MR spectroscopy (MRS), respectively. The serum metabolic profile was obtained using proton NMR spectroscopy. NMR spectra were integrated into seven integration regions, which reflect relative metabolites. Results: A significant metabolic disorder symptom appeared in the overweight and obese group, and increased lipid deposition occurred in the abdomen, hepatocytes, and muscles that were statistically significant. Overall, the visceral fat depots had a marked influence on dyslipidemia biomarkers, blood triglyceride (r = 0.592, p < 0.001), and high-density lipoprotein cholesterol (r = −0.484, p < 0.001). Intrahepatocellular lipid was associated with diabetes predictors for hemoglobin (HbA1c%; r = 0.379, p < 0.001) and for fasting blood sugar (r = 0.333, p < 0.05). The lipid signals in serum triglyceride and glucose signals gave similar correspondence to biochemical lipid profiles. Conclusions: This study proves the association between alteration in metabolome in young adults, which is the key population for early prevention of obesity and metabolic syndrome. This study suggests that dyslipidemia prevalence is influenced mainly by the visceral fat depot, and liver fat depot is a key determinant for glucose metabolism and hyperglycemia. Moreover, noninvasive advanced molecular imaging completely elucidated the impact of fat distribution on the anthropometric and laboratory parameters, especially indices of the metabolic syndrome biomarkers in young adults.

Lower limit of body fat in healthy active men

1994 ◽  
Vol 77 (2) ◽  
pp. 933-940 ◽  
Author(s):  
K. E. Friedl ◽  
R. J. Moore ◽  
L. E. Martinez-Lopez ◽  
J. A. Vogel ◽  
E. W. Askew ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Lower Limit ◽  
Body Fat ◽  
Fat Mass ◽  
Subcutaneous Fat ◽  
Fat Free Mass ◽  
Energy Deficit ◽  
Strenuous Exercise ◽  
Healthy Men

We examined body composition changes in 55 normal young men during an 8-wk Army combat leadership training course involving strenuous exercise and low energy intake, with an estimated energy deficit of 5.0 +/- 2.0 MJ/day and a resultant 15.7 +/- 3.1% weight loss. Percent body fat (BF) measured by dual-energy X-ray absorptiometry (DEXA) averaged 14.3% (range 6–26%) and 5.8 +/- 1.8% (range 4–11%) at the beginning and end of the course, respectively. Men who achieved a minimum percent BF (4–6%) by 6 wk demonstrated only small additional total and subcutaneous fat losses in the final 2 wk and sacrificed increasingly larger proportions of fat-free mass. Percent BF estimated from skinfold thicknesses reflected relative changes in fat mass, although actual percent BF was overestimated. Instead of reaching a plateau after fat stores were substantially depleted, abdominal, hip, and thigh girths continued to decline with body weight loss. Final percent BF for the leanest men was similar to that observed after a 25% body weight reduction in the 1950 Minnesota study (5.2% by underwater weighting), and height-corrected final fat mass was the same (1.0 +/- 0.2 vs. 0.9 +/- 0.7 kg fat/m2), suggesting that these values represent a minimal body fat content in healthy men and that weight loss subsequent to achieving this level is contributed from the fat-free mass. Our results suggest that 4–6% BF or approximately 2.5 kg fat represents the lower limit for healthy men, as assessed by DEXA or by underwater weighing.

The increase in abdominal subcutaneous fat depot is an independent factor to determine the glycemic control after rosiglitazone treatment

2007 ◽  
Vol 157 (2) ◽  
pp. 167-174 ◽  
Author(s):  
Soo-Kyung Kim ◽  
Kyu-Yeon Hur ◽  
Hae-Jin Kim ◽  
Wan-Sub Shim ◽  
Chul-Woo Ahn ◽  
...  
Keyword(s):  
Glycemic Control ◽  
Visceral Fat ◽  
Subcutaneous Fat ◽  
Fat Distribution ◽  
The Body ◽  
Diabetic Patients ◽  
Independent Factor ◽  
Type 2 Diabetic Patients ◽  
Rosiglitazone Treatment ◽  
Fat Depot

Objective: The goal was to investigate the interrelationships between the hypoglycemic effects of rosiglitazone and the changes in the regional adiposity of type 2 diabetic patients. Design and methods: We added rosiglitazone (4 mg/day) to 173 diabetic patients (111 males and 62 females) already taking a stable dose of conventional antidiabetic medications except for thiazolidinediones. The abdominal fat distribution was assessed by ultrasonography at baseline and 12 weeks later. Using ultrasonographic images, the s.c. and visceral fat thickness (SFT and VFT respectively) were measured. Results: Rosiglitazone treatment for 3 months improved the glycemic control. However, the response to rosiglitazone was no more than 36.4%; the deterioration of the glycemic control was found in 16.8% of subjects. In addition, rosiglitazone treatment significantly increased the body fat mass, especially the s.c. fat. However that did not alter the visceral fat content. The percentage changes in fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c) concentrations after treatment were inversely correlated with the increase in SFT (r=−0.327 and −0.353, P<0.001 respectively) and/or body weight (r=−0.316 and −0.327, P<0.001 respectively). Multiple regression analysis revealed that the improvement in the FPG after rosiglitazone treatment was correlated with the baseline FPG (P<0.001) and the change in the SFT (P=0.019), and the reduction in the HbA1c was related with the baseline FPG (P=0.003) and HbA1c (P<0.001) and the changes in the SFT (P=0.010) or VFT (P=0.013). Conclusions: The increase in the s.c. fat depot after rosiglitazone treatment may be an independent factor that determines the hypoglycemic efficacy.

scholarly journals Subcutaneous fat mass is associated with genetic risk scores related to proinflammatory cytokine signaling and interact with physical activity in middle-aged obese adults

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
James W. Daily ◽  
Hye Jeong Yang ◽  
Meiling Liu ◽  
Min Jung Kim ◽  
Sunmin Park
Keyword(s):  
Physical Activity ◽  
Fat Mass ◽  
Visceral Fat ◽  
Genetic Variants ◽  
Genetic Risk ◽  
Odds Ratio ◽  
Subcutaneous Fat ◽  
Risk Scores ◽  
Obese Adults ◽  
High Physical Activity

Abstract Background and aims Subcutaneous fat mass is negatively correlated with atherogenic risk factors, but its putative benefits remain controversial. We hypothesized that genetic variants that influence subcutaneous fat mass would modulate lipid and glucose metabolism and have interactions with lifestyles in Korean middle-aged adults with high visceral fat. Materials and methods Subcutaneous fat mass was categorized by dividing the average of subscapular skin-fold thickness by BMI and its cutoff point was 1.2. Waist circumferences were used for representing visceral fat mass with Asian cutoff points. GWAS of subjects aged 40–65 years with high visceral fat (n = 3303) were conducted and the best gene-gene interactions from the genetic variants related to subcutaneous fat were selected and explored using the generalized multifactor dimensionality reduction. Genetic risk scores (GRS) were calculated by weighted GRS that was divided into low, medium and high groups. Results Subjects with high subcutaneous fat did not have dyslipidemia compared with those with low subcutaneous fat, although both subject groups had similar amounts of total fat. The best model to influence subcutaneous fat included IL17A_rs4711998, ADCY2_rs326149, ESRRG_rs4846514, CYFIP2_rs733730, TCF7L2_rs7917983, ZNF766_rs41497444 and TGFBR3_rs7526590. The odds ratio (OR) for increasing subcutaneous fat was higher by 2.232 folds in the high-GRS group, after adjusting for covariates. However, total and LDL cholesterol, triglyceride and C-reactive protein concentrations in the circulation were not associated with GRS. Subjects with high-GRS had higher serum HDL cholesterol levels than those with low-GRS. Physical activity and GRS had an interaction with subcutaneous fat. In subjects with low physical activity, the odds ratio for high subcutaneous fat increased by 2.232, but subcutaneous fat deposition was not affected in the high-GRS group with high physical activity. Conclusion Obese adults with high-GRS had more subcutaneous fat, but they did not show more dyslipidemia and inflammation compared to low-GRS. High physical activity prevented subcutaneous fat deposition in subjects with high GRS for subcutaneous fat.

Visceral Fat: Higher Responsiveness of Fat Mass and Gene Expression to Calorie Restriction than Subcutaneous Fat

2003 ◽  
Vol 228 (10) ◽  
pp. 1118-1123 ◽  
Author(s):  
Yin Li ◽  
Hideaki Bujo ◽  
Kazuo Takahashi ◽  
Manabu Shibasaki ◽  
Yanjuan Zhu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Calorie Restriction ◽  
Fat Mass ◽  
Visceral Fat ◽  
Subcutaneous Fat

scholarly journals Relationships between fat depots and body condition score or tail fatness in the Rasa Aragonesa breed

1989 ◽  
Vol 49 (2) ◽  
pp. 275-280 ◽  
Author(s):  
A. Teixeira ◽  
R. Delfa ◽  
F. Colomer-Rocher
Keyword(s):  
Body Fat ◽  
Body Condition ◽  
Body Condition Score ◽  
Live Weight ◽  
Fat Depots ◽  
Condition Score ◽  
Total Fat ◽  
Total Body ◽  
Fat Depot ◽  
The Individual

ABSTRACTThe relationships between body fat depots and body condition score (BCS) were determined in 52 adult Rasa Aragonesa ewes aged 10 (s.d. 2) years and ranging in BCS from 1·5 to 4·5. BCS of each ewe was assessed by three people, the repeatability within individuals being 90% and between individuals 80%. The ewes were weighed before slaughter. After slaughter the omental, mesenteric, kidney and pelvic fat were separated and weighed. The fat of the left side of the carcass was separated into subcutaneous and intermuscular depots. The relationship between live weight and BCS was semilogarithmic and those between fat depots and BCS were logarithmic. Regression analysis was also used to describe the relationships between the various fat depots and BCS or live weight. Of the variation in total fat weight, proportionately 0·90 was accounted for by variations in BCS, while 0·84 was accounted for by variations in live weight. For individual fat depots proportionately 0·86 to 0·90 of the variation was accounted for by variation in BCS and 0·69 to 0·79 by variation in live weight. BCS was a better predictor than live weight of the weight of both total body fat and the individual fat depots.A curvilinear regression between BCS and live weight showed that the increases in live weight for a unit change in BCS was 7, 10, 12 and 16 kg for each one point increase in BCS from 1 to 5 respectively.The tail fat depot (tail fatness score) was assessed in the same ewes by score on a three-point scale. Of the variation in the weight of individual fat depots, proportionately 0·79 to 0·86 was accounted for by variation in tail fatness score. Thus the tail fatness score could be used as an additional method of assessing body condition in the Aragonesa breed.

scholarly journals Lipid metabolism in women

2004 ◽  
Vol 63 (1) ◽  
pp. 153-160 ◽  
Author(s):  
Christine M. Williams
Keyword(s):  
Adipose Tissue ◽  
Cardiovascular Risk ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Body Fat ◽  
Adrenergic Receptors ◽  
Subcutaneous Fat ◽  
Fatty Acid Uptake ◽  
Acid Uptake ◽  
Fat Depots

Differences in whole-body lipid metabolism between men and women are indicated by lower-body fat accumulation in women but more marked accumulation of fat in the intra-abdominal visceral fat depots of men. Circulating blood lipid concentrations also show gender-related differences. These differences are most marked in premenopausal women, in whom total cholesterol, LDL-cholesterol and triacylglycerol concentrations are lower and HDL-cholesterol concentration is higher than in men. Tendency to accumulate body fat in intra-abdominal fat stores is linked to increased risk of CVD, metabolic syndrome, diabetes and other insulin-resistant states. Differential regional regulation of adipose tissue lipolysis and lipogenesis must underlie gender-related differences in the tendency to accumulate fat in specific fat depots. However, empirical data to support current hypotheses remain limited at the present time because of the demanding and specialist nature of the methods used to study adipose tissue metabolism in human subjects. In vitro and in vivo data show greater lipolytic sensitivity of abdominal subcutaneous fat and lesser lipolytic sensitivity of femoral and gluteal subcutaneous fat in women than in men. These differences appear to be due to fewer inhibitory α adrenergic receptors in abdominal regions and greater α adrenergic receptors in gluteal and femoral regions in women than in men. There do not appear to be major gender-related differences in rates of fatty acid uptake (lipogenesis) in different subcutaneous adipose tissue regions. In visceral fat rates of both lipolysis and lipogenesis appear to be greater in men than in women; higher rates of lipolysis may be due to fewer α adrenergic receptors in this fat depot in men. Fatty acid uptake into this depot in the postprandial period is approximately 7-fold higher in men than in women. Triacylglycerol concentrations appear to be a stronger cardiovascular risk factor in women than in men, with particular implications for cardiovascular risk in diabetic women. The increased triacylglycerol concentrations observed in women taking hormone-replacement therapy (HRT) may explain the paradoxical findings of increased rates of CVD in women taking HRT that have been reported from recent primary and secondary prevention trials of HRT.

scholarly journals Inhibition of Angiopoietin-Like 3 (ANGPTL3) Reduces Adipose Tissue Insulin Resistance in Patients With Familial Partial Lipodystrophy

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A50-A51
Author(s):  
Maria Cristina Foss de Freitas ◽  
Baris Akinci ◽  
Adam Neidert ◽  
Rita Hench ◽  
Elif A Oral
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Body Fat ◽  
Fat Mass ◽  
Subcutaneous Fat ◽  
Hormonal Changes ◽  
Loss Of Function ◽  
Partial Lipodystrophy ◽  
Number Of Patients ◽  
Familial Partial Lipodystrophy

Abstract Familial partial lipodystrophy (FPLD) is a rare disease characterized by selective loss of peripheral subcutaneous fat, usually affecting the trunk and limbs, but preservation in other areas, such as the face and neck. It is usually associated with dyslipidemia and diabetes mellitus, and currently, there are no approved specific therapies for this disease in the US. Reductions in circulating levels of ANGPTL3 either by homologous loss-of-function mutations in humans or by pharmacological inhibition in rodents are associated with reductions in triglyceride (and other atherogenic lipid) levels and protect from atherosclerosis, making it an attractive target for patients with FPLD and metabolic dyslipidemia. We performed a proof-of-concept study to assess the early efficacy and safety of targeting ANGPTL3 via antisense oligonucleotide ISIS-703802 (vupanorsen) in a small number of patients with FPLD. Four patients with FPLD (3F/1M; age range: 39–48; 1 with LMNA R482Q, 1 with LMNA R584H, and 2 with no causative genetic variant), diabetes (HbA1c&gt;6.5%) and hypertriglyceridemia (&gt;250 mg/dL at screening) were included. Patients received the study drug at a subcutaneous dose of 20 mg weekly for 26 weeks. The primary endpoint was the change in triglycerides at week 27. Other end-points of interest measured at the same time points included insulin secretion, sensitivity, lipid and hormonal changes in response to a 5 hour long mixed meal test and body composition measured by dual energy absorptiometry (DEXA). Treatment resulted in a 59.9±26.3 (mean±SD) % of reduction in triglycerides, 54.7±9.8% of reduction in serum ANGPTL3 levels and 50.8±27.4% of reduction in ApoCIII. Treatment with vupanorsen led to a reduction of 209.3±120.4 in adipose tissue insulin resistance (ADIPO-IR) from a baseline of 470.3±114.3 and the area under the curve (AUC) for circulating free fatty acid levels were decreased by 32.1±21.4 mmol/L/min from a baseline of 215.8±55.2 mmol/L/min. Glucose AUC and triglyceride AUC also decreased after treatment (-14.0±5.2 and -60.1±26.5 mg/dL/min, respectively). Analyzing body fat distribution using DEXA, we observed that the fat mass index (FMI) and trunk mass index (TMI) did not change from baseline, but the ratio of total fat mass/ fat mass from limbs decreased by 10.7±12.2. These data show a tendency for redistribution of central body fat to limbs. There were numerous adverse events observed that were related to common serious complications associated with diabetes and FPLD. Although limited, these results suggest that targeting ANGPTL3 with vupanorsen in patients with FPLD may have a therapeutic role by addressing multiple problems.

Sign in / Sign up

Export Citation Format

Share Document