scholarly journals The DGAT2 gene is a candidate for the dissociation between fatty liver and insulin resistance in humans

2009 ◽  
Vol 116 (6) ◽  
pp. 531-537 ◽  
Author(s):  
Konstantinos Kantartzis ◽  
Fausto Machicao ◽  
Jürgen Machann ◽  
Fritz Schick ◽  
Andreas Fritsche ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Fatty Liver ◽  
Body Fat ◽  
Visceral Fat ◽  
Magnetic Resonance Tomography ◽  
Liver Fat ◽  
Oral Glucose ◽  
Total Body Fat ◽  
Total Body

The enzyme DGAT (acyl-CoA:diacylglycerol acyltransferase) catalyses the final step of triacylglycerol (triglyceride) synthesis. Mice overexpressing hepatic DGAT2 fed a high-fat diet develop fatty liver, but not insulin resistance, suggesting that DGAT2 induces a dissociation between fatty liver and insulin resistance. In the present study, we investigated whether such a phenotype also exists in humans. For this purpose, we determined the relationships between genetic variability in the DGAT2 gene with changes in liver fat and insulin sensitivity in 187 extensively phenotyped subjects during a lifestyle intervention programme with diet modification and an increase in physical activity. Changes in body fat composition [MR (magnetic resonance) tomography], liver fat and intramyocellular fat (1H-MR spectroscopy) and insulin sensitivity [OGTT (oral glucose tolerance test) and euglycaemic–hyperinsulinaemic clamp] were determined after 9 months of intervention. A change in insulin sensitivity correlated inversely with changes in total body fat, visceral fat, intramyocellular fat and liver fat (OGTT, all P<0.05; clamp, all P≤0.03). Changes in total body fat, visceral fat and intramyocellular fat were not different between the genotypes of the SNPs (single nucleotide polymorphisms) rs10899116 C>T and rs1944438 C>T (all P≥0.39) of the DGAT2 gene. However, individuals carrying two or one copies of the minor T allele of SNP rs1944438 had a smaller decrease in liver fat (−17±10 and −24±5%; values are means±S.E.M.) compared with subjects homozygous for the C allele (−39±7%; P=0.008). In contrast, changes in insulin sensitivity were not different among the genotypes (OGTT, P=0.76; clamp, P=0.53). In conclusion, our findings suggest that DGAT2 mediates the dissociation between fatty liver and insulin resistance in humans. This finding may be important in the prevention and treatment of insulin resistance and Type 2 diabetes in subjects with fatty liver.

scholarly journals Change in Visceral Fat and Total Body Fat and the Effect on Cardiometabolic Risk Factors During Transgender Hormone Therapy

2021 ◽  
Author(s):  
Maartje Klaver ◽  
Daan van Velzen ◽  
Christel de Blok ◽  
Nienke Nota ◽  
Chantal Wiepjes ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Hormone Therapy ◽  
Body Fat ◽  
Visceral Fat ◽  
Cardiometabolic Risk ◽  
Trans Men ◽  
Total Body Fat ◽  
In Trans ◽  
Trans Women ◽  
Total Body

Abstract Introduction Excess visceral fat increases the risk of type 2 diabetes and cardiovascular disease and is influenced by sex hormones. Our aim was to investigate changes in visceral fat and the ratio of visceral fat to total body fat (VAT/TBF) and their associations with changes in lipids and insulin resistance after 1 year of hormone therapy in trans persons. Methods In 179 trans women and 162 trans men, changes in total body and visceral fat estimated with dual-energy X-ray absorptiometry before and after 1 year of hormone therapy were related to lipids and insulin resistance [homeostatic model assessment of insulin resistance (HOMA-IR)] with linear regression analysis. Results In trans women, total body fat increased by 4.0 kg (95% CI 3.4, 4.7), while the amount of visceral fat did not change (−2 grams; 95% CI −15, 11), albeit with a large range from −318 to 281, resulting in a decrease in the VAT/TBF ratio of 17% (95% CI 15, 19). In trans men, total body fat decreased with 2.8 kg (95% CI 2.2, 3.5), while the amount of visceral fat did not change (3 g; 95% CI −10, 16; range −372, 311), increasing the VAT/TBF ratio by 14% (95% CI 10, 17). In both groups, VAT/TBF was not associated with changes in blood lipids or HOMA-IR. Conclusions Hormone therapy in trans women and trans men resulted in changes in VAT/TBF, mainly due to changes in total body fat and were unrelated to changes in cardiometabolic risk factors, which suggests that any unfavorable cardiometabolic effects of hormone therapy are not mediated by changes in visceral fat or VAT/TBF.

scholarly journals Circulating Levels of FGF-21 in Obese Youth: Associations With Liver Fat Content and Markers of Liver Damage

2013 ◽  
Vol 98 (7) ◽  
pp. 2993-3000 ◽  
Author(s):  
Cosimo Giannini ◽  
Ariel E. Feldstein ◽  
Nicola Santoro ◽  
Grace Kim ◽  
Romy Kursawe ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Fatty Liver ◽  
Visceral Fat ◽  
Fat Content ◽  
Liver Fat ◽  
Oral Glucose ◽  
Cytokeratin 18 ◽  
Obese Adolescents ◽  
Obese Youth ◽  
Hepatic Fat

Objective: Fibroblast growth factor (FGF)-21 is highly expressed in the liver and regulates glucose and lipid metabolism in rodents. The effects of obesity and fatty liver on circulating FGF-21 levels have been described mainly in adults. Herein, we measured plasma FGF-21 levels in lean and obese adolescents with low and high hepatic fat content (HFF% &lt;5.5% and HFF% ≥5.5%, respectively) and explored their relationship with hepatic fat content, measures of hepatic apoptosis, and insulin sensitivity. Methods: A total of 217 lean and obese adolescents with both low and high HFF% (lean = 31; obese low HFF% = 107; and obese high HFF% = 79) underwent an oral glucose tolerance test, a fast gradient magnetic resonance imaging to measure the %HFF and abdominal fat distribution. Cytokeratin 18 levels were measured as a biomarker of liver apoptosis. A subset of adolescents underwent a 2-step hyperinsulinemic-euglycemic clamp, and a liver biopsy (N = 14), to assess insulin sensitivity and steatohepatitis, respectively. Results: Compared to controls, FGF-21 levels were higher in obese youth, especially in those with high HFF (P &lt; .001). FGF-21 significantly correlated with adiposity indexes (P &lt; .001), visceral fat (r2 = 0.240, P &lt; .001), hepatic fat content (r2 = 0.278, P &lt; .001), cytokeratin 18 (r2 = 0.217, P &lt; .001), and alanine aminotransferase (r2 = .164, P &lt; .001). In subjects with steatoheaptitis, FGF-21 levels significantly correlated with the nonalcoholic fatty liver disease activity score (r2 = 0.27, P = .04). Stepwise regression analysis indicated that these relationships are independent of body mass index, visceral fat, and insulin sensitivity. An inverse correlation was documented with insulin, hepatic resistance indexes, and adipose resistance indexes, which disappeared after adjusting for hepatic fat content. Conclusions: Plasma FGF-21 levels are increased in obese adolescents, particularly in those with fatty liver. FGF-21 concentrations significantly and independently correlate with hepatic fat content and markers of hepatic apoptosis in obese youths.

scholarly journals Hepatic Insulin Extraction in NAFLD Is Related to Insulin Resistance Rather Than Liver Fat Content

2018 ◽  
Vol 104 (5) ◽  
pp. 1855-1865 ◽  
Author(s):  
Kristina M Utzschneider ◽  
Steven E Kahn ◽  
David C Polidori
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Body Fat ◽  
Subcutaneous Fat ◽  
Insulin Clearance ◽  
Liver Fat ◽  
Glucose Disposal ◽  
Oral Glucose ◽  
Cross Sectional ◽  
Hepatic Insulin Extraction

Abstract Context Total insulin clearance is decreased in nonalcoholic fatty liver disease (NAFLD), but the relationship between liver fat and hepatic insulin extraction (HIE) is unknown. Objective This cross-sectional study addresses the hypothesis that HIE is reduced in NAFLD and investigates metabolic and/or anthropometric characteristics most closely associated with insulin clearance. Participants Nondiabetic subjects with NAFLD (n = 13) and age- and body mass index (BMI)-matched controls with normal liver enzymes (n = 15) underwent abdominal CT, dual-energy X-ray absorptiometry, oral glucose tolerance test (OGTT), and labeled two-step hyperinsulinemic-euglycemic clamps. Outcome Measurements Liver fat was estimated by the CT liver/spleen ratio. Hepatic and extrahepatic insulin clearances were modeled using clamp and OGTT data. Results Extrahepatic insulin clearance and HIE were not different between NAFLD and controls and did not correlate with liver fat. HIE was positively correlated with insulin sensitivity [rate of glucose disposal (Rd; low r = +0.7, P &lt; 0.001; high r = +0.6, P = 0.001), adiponectin (r = +0.55, P = 0.004), and insulin-mediated suppression of clamp nonesterified free fatty acid (NEFA; r = +0.67, P &lt; 0.001)] but was not associated with fasting NEFA, insulin-mediated suppression of glucose production, or measures of adiposity. Extrahepatic insulin clearance was positively associated with percent body fat (r = +0.44, P = 0.02) and subcutaneous fat (r = +0.42, P = 0.03) but not BMI, intra-abdominal fat, liver fat, Rd, adiponectin, or NEFA. Conclusions HIE is not directly associated with hepatic steatosis but is associated with muscle and adipose tissue insulin resistance. The data suggest differential regulation of insulin clearance with extrahepatic insulin clearance being associated with body fat and not insulin sensitivity.

Subcutaneous lipectomy causes a metabolic syndrome in hamsters

2000 ◽  
Vol 279 (3) ◽  
pp. R936-R943 ◽  
Author(s):  
R. V. Weber ◽  
M. C. Buckley ◽  
S. K. Fried ◽  
J. G. Kral
Keyword(s):  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Body Fat ◽  
Liver Fat ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Liver Fat Content ◽  
Serum Triglycerides ◽  
Total Body Fat ◽  
Total Body

The insulin resistance syndrome X is related to excess intra-abdominal adipose tissue. With lipectomy of >50% of subcutaneous adipose tissue (SQAT) in nonhibernating, adult female Syrian hamsters on high-fat (HF; 50 calorie%) diet and measurements of oral glucose tolerance, oral [14C]oleic acid disposal, serum triglycerides, serum leptin, liver fat, perirenal (PR) adipose tissue cellularity, and body composition, we studied the role of SQAT. Sham-operated (S) animals on HF or low-fat (LF; 12.5 calorie%) diets served as controls. After 3 mo there was no visible regrowth of SQAT but HF diet led to similar levels of body weight and body fat in lipectomized and sham-operated animals. Lipectomized (L) animals had more intra-abdominal fat as a percentage of total body fat, higher insulinemic index, a strong trend toward increased liver fat content, and markedly elevated serum triglycerides compared with S-HF and S-LF. Liver and PR adipose tissue uptake of fatty acid were similar in L-HF and S-HF but reduced vs. S-LF, and were inversely correlated with liver fat content and insulin sums during the oral glucose tolerance test. In summary, lipectomy of SQAT led to compensatory fat accumulation implying regulation of total body fat mass. In conjunction with HF diet these lipectomized hamsters developed a metabolic syndrome with significant hypertriglyceridemia, relative increase in intra-abdominal fat, and insulin resistance. We propose that SQAT, via disposal and storage of excess ingested energy, acts as a metabolic sink and protects against the metabolic syndrome of obesity.

scholarly journals The Association between Adult Weight Gain and Insulin Resistance at Middle Age: Mediation by Visceral Fat and Liver Fat

2019 ◽  
Vol 8 (10) ◽  
pp. 1559 ◽  
Author(s):  
Inge Verkouter ◽  
Raymond Noordam ◽  
Saskia le Cessie ◽  
Rob M. van Dam ◽  
Hildo J. Lamb ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Weight Gain ◽  
Weight Change ◽  
Visceral Fat ◽  
Middle Age ◽  
Liver Fat ◽  
Adult Weight ◽  
Total Body Fat ◽  
Total Body

We aimed to investigate the role of the amount of visceral fat and liver fat in the association between adult weight change and insulin resistance at middle age. In the Netherlands Epidemiology of Obesity study, adult weight change was calculated with recalled body weight at age 20 years and measured body weight at middle age. Measures of insulin resistance were calculated using both fasting and postprandial glucose and insulin concentrations. Visceral fat was assessed by magnetic resonance (MR) imaging and liver fat by proton-MR spectroscopy (N = 1758). We examined the association between adult weight change and insulin resistance with linear regression, adjusted for confounding factors. To investigate mediation, we additionally adjusted for total body fat, visceral fat, and liver fat. In participants who gained ≥50% of body weight during adulthood, homeostatic model assessment for insulin resistance (HOMA-IR) was 3.22 (95% CI 2.76; 3.77) times higher than in weight maintainers. In a joint model, total body fat mediated this association for 8.1% (95% CI −9.2; 25.4), visceral fat for 32.0% (18.6; 45.4%) and liver fat for 22.5% (15.0; 30.1). The association between adult weight gain and insulin resistance at middle age is largely mediated by both visceral fat and liver fat.

scholarly journals Adipose Tissue Adiponectin Production and Adiponectin Serum Concentration in Human Obesity and Insulin Resistance

2004 ◽  
Vol 89 (3) ◽  
pp. 1391-1396 ◽  
Author(s):  
Johan Hoffstedt ◽  
Elisabet Arvidsson ◽  
Eva Sjölin ◽  
Kerstin Wåhlén ◽  
Peter Arner
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Serum Concentration ◽  
Body Fat ◽  
Secretion Rate ◽  
Human Obesity ◽  
Total Body Fat ◽  
Total Body

Abstract The role of adiponectin production for the circulating protein concentration in human obesity and insulin resistance is unclear. We measured serum concentration and sc adipose tissue secretion rate of adiponectin in 77 obese and 23 nonobese women with a varying degree of insulin sensitivity. The serum adiponectin concentration was similar in both groups. In obesity, adiponectin adipose tissue secretion rate per weight unit was reduced by 30% (P = 0.01), whereas total body fat secretion rate was increased by 100% (P &lt; 0.0001). In the group being most insulin resistant (1/3), serum concentration (P &lt; 0.001) and adipose tissue secretion rate per tissue weight (P &lt; 0.05) were reduced, whereas total body fat secretion rate was increased (P &lt; 0.01), by about 30%. The adipose tissue secretion rate of adiponectin was related to the serum concentration (P = 0.005) but explained only about 10% of the interindividual variation in circulating adiponectin and insulin sensitivity. The plasma adiponectin half life was long, 2.5 h. In conclusion, the role of protein secretion for the circulating concentration of adiponectin and insulin sensitivity under these conditions is minor because adiponectin turnover rate is slow. Although increased in obesity and insulin resistance, total body production of adiponectin is insufficient to raise the circulating concentration, may be due to reduced secretion rate per tissue unit.

scholarly journals Regulation of glucose metabolism in nondiabetic, metabolically obese normal-weight Asians

2018 ◽  
Vol 314 (5) ◽  
pp. E494-E502 ◽  
Author(s):  
Cherlyn Ding ◽  
Zhiling Chan ◽  
Yu Chung Chooi ◽  
John Choo ◽  
Suresh Anand Sadananthan ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Body Fat ◽  
Postprandial Glucose ◽  
Normal Weight ◽  
Increased Risk ◽  
Total Body Fat ◽  
Metabolically Obese Normal Weight ◽  
Total Body

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.

Leptin: a significant indicator of total body fat but not of visceral fat and insulin insensitivity in African-American women

Diabetes ◽  
1996 ◽  
Vol 45 (11) ◽  
pp. 1635-1637 ◽  
Author(s):  
A. Dua ◽  
M. I. Hennes ◽  
R. G. Hoffmann ◽  
D. L. Maas ◽  
G. R. Krakower ◽  
...  
Keyword(s):  
African American ◽  
African American Women ◽  
Body Fat ◽  
Visceral Fat ◽  
American Women ◽  
Total Body Fat ◽  
Total Body ◽  
Insulin Insensitivity

scholarly journals Body mass index and waist circumference are better predictors of insulin resistance than total body fat percentage in middle-aged and elderly Taiwanese

Medicine ◽  
2017 ◽  
Vol 96 (39) ◽  
pp. e8126 ◽  
Author(s):  
Yiu-Hua Cheng ◽  
Yu-Chung Tsao ◽  
I-Shiang Tzeng ◽  
Hai-Hua Chuang ◽  
Wen-Cheng Li ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Mass Index ◽  
Waist Circumference ◽  
Body Mass ◽  
Body Fat ◽  
Body Fat Percentage ◽  
Middle Aged ◽  
Fat Percentage ◽  
Total Body Fat ◽  
Total Body
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