Visceral fat and insulin resistance — causative or correlative?

The association between abdominal fat accumulation and risk of chronic diseases, including type II diabetes and coronary heart disease, has long been recognized. Insulin resistance may be a key factor in this link. Many studies have pointed to an association between insulin resistance and intra-abdominal fat accumulation (visceral obesity). However there is no clear proof of a causal link between visceral fat accumulation and insulin resistance. In assessing the probability of a causal link, it is useful to consider potential mechanisms. One such potential causal link is the release of non-esterified fatty acids from visceral fat into the portal vein, so that they have direct effects on hepatic metabolism. Visceral fat has been shown in many studies to exhibit a high rate of lipolysis compared with subcutaneous fat depots. However, if the idea that visceral fat releases fatty acids into the portal vein at a high rate is examined critically, a number of difficulties appear. Not least of these is the fact that continued high rates of lipolysis should lead to the disappearance of the visceral fat depot, unless these high rates of fat mobilization are matched by high rates of fat deposition. There is far less evidence for high rates of fat deposition in visceral adipose tissue, and some contrary evidence. Evidence for high rates of visceral lipolysis in vivo from studies involving catheterization of the portal vein is not strong. If this potential link is discounted, then other reasons for the relationship between visceral fat and insulin resistance must be considered. One is that there is no direct causal link, but both co-correlate with some other variable. A possibility is that this other variable is subcutaneous abdominal fat, which usually outweighs intra-abdominal fat several-fold. Subcutaneous fat probably plays the major role in determining systemic plasma non-esterified fatty acid concentrations, which are relevant in determining insulin resistance. In conclusion, there is at present no proof of a causal link between visceral fat accumulation and insulin resistance, or the associated metabolic syndrome. The possibility of co-correlation with some other factor, such as subcutaneous abdominal fat accumulation, must not be forgotten.

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Fatty Liver Is a Better Marker of Muscle Insulin Resistance than Visceral Fat Accumulation in Nonobese Japanese Men

Diabetes ◽

10.2337/db18-1854-p ◽

2018 ◽

Vol 67 (Supplement 1) ◽

pp. 1854-P

Author(s):

SATOSHI KADOWAKI ◽

YOSHIFUMI TAMURA ◽

YUKI SOMEYA ◽

KAGEUMI TAKENO ◽

TAKASHI FUNAYAMA ◽

...

Keyword(s):

Insulin Resistance ◽

Fatty Liver ◽

Visceral Fat ◽

Japanese Men ◽

Muscle Insulin Resistance ◽

Fat Accumulation ◽

Visceral Fat Accumulation

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Relationships between Composition of Major Fatty Acids and Fat Distribution and Insulin Resistance in Japanese

Journal of Diabetes Research ◽

10.1155/2017/1567467 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Chikako Fujii ◽

Toshihide Kawai ◽

Koichiro Azuma ◽

Yuko Oguma ◽

Fuminori Katsukawa ◽

...

Keyword(s):

Insulin Resistance ◽

Fatty Acids ◽

Linoleic Acid ◽

Glucose Tolerance ◽

Visceral Fat ◽

Subcutaneous Fat ◽

Fat Distribution ◽

Normal Subjects ◽

Metabolic Parameters ◽

Visceral Fat Area

Objective. The aim of this study was to evaluate the relationships between the composition of free fatty acids (FFAs) and metabolic parameters, including body fat distribution, in Japanese.Methods. The study subjects were 111 Japanese patients (54 males, 57 females). Metabolic parameters and visceral and subcutaneous fat areas as determined by CT scanning at the umbilical level were measured. Glucose tolerance test (GTT) was performed by administering 75 g glucose orally.Results. The percentage of linoleic acid (C18:2), the greatest constituent among FFAs, was negatively correlated with visceral fat area (r=−0.411,p<0.0001), fasting glucose (r=−0.330,p<0.0001), HbA1c (r=−0.231,p=0.0146), and systolic blood pressure (r=−0.224,p=0.0184). Linoleic acid percentage was also significantly negatively correlated with HOMA-IR (r=−0.416,p<0.0001) by simple correlation. Based on the findings of OGTT, the 111 subjects were classified into three groups: 33 with normal glucose tolerance, 71 with impaired glucose tolerance (IGT), and 7 diabetic subjects. The percentage of serum linoleic acid in diabetic subjects was significantly lower than that in normal subjects.Conclusion. We conclude that serum linoleic acid level is negatively correlated with the accumulation of visceral fat in relation to a reduction of insulin resistance in Japanese subjects.

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Visceral fat accumulation in obese subjects: relation to energy expenditure and response to weight loss

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1992.263.5.e913 ◽

1992 ◽

Vol 263 (5) ◽

pp. E913-E919 ◽

Cited By ~ 6

Author(s):

R. Leenen ◽

K. van der Kooy ◽

P. Deurenberg ◽

J. C. Seidell ◽

J. A. Weststrate ◽

...

Keyword(s):

Weight Loss ◽

Energy Expenditure ◽

Visceral Fat ◽

Resting Metabolic Rate ◽

Subcutaneous Fat ◽

Premenopausal Women ◽

Energy Deficit ◽

Fat Accumulation ◽

Visceral Fat Accumulation ◽

Obese Subjects

Seventy-eight healthy obese subjects, 40 premenopausal women and 38 men aged 27-51 yr received a 4.2 MJ/day energy-deficit diet for 13 wk. Resting metabolic rate (RMR) and diet-induced thermogenesis (DIT) were measured by indirect calorimetry. Abdominal subcutaneous and visceral fat areas were calculated from magnetic resonance imaging scans before and after weight loss. Before weight loss, visceral fat accumulation was positively correlated with higher levels of RMR (P < 0.05) and DIT (P < 0.01) in women but not in men. The mean weight reduction was 12.2 +/- 3.5 (SD) kg. In men but not in women, an initially large visceral fat depot was associated with a reduced loss of weight and total fat mass (P < 0.05). Within each sex, an initial abundance of visceral fat was significantly related to a larger loss of visceral fat (P < 0.001) and in men to a smaller loss of subcutaneous fat (P < 0.05). These results suggest that there may be gender differences in the associations between visceral fat accumulation and components of energy expenditure (RMR and DIT) in obese subjects. Obese subjects with an initial abundance of visceral fat do not lose more body weight but more visceral fat than subjects with less visceral fat.

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Lower Birth Weight and Visceral Fat Accumulation Are Related to Hyperinsulinemia and Insulin Resistance in Obese Japanese Children

Hypertension Research ◽

10.1291/hypres.28.529 ◽

2005 ◽

Vol 28 (6) ◽

pp. 529-536 ◽

Cited By ~ 25

Author(s):

Yukie TANAKA ◽

Toru KIKUCHI ◽

Keisuke NAGASAKI ◽

Makoto HIURA ◽

Yohei OGAWA ◽

...

Keyword(s):

Insulin Resistance ◽

Birth Weight ◽

Visceral Fat ◽

Japanese Children ◽

Fat Accumulation ◽

Lower Birth Weight ◽

Visceral Fat Accumulation

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Exercise-induced reversal of insulin resistance in obese elderly is associated with reduced visceral fat

Journal of Applied Physiology ◽

10.1152/japplphysiol.01336.2005 ◽

2006 ◽

Vol 100 (5) ◽

pp. 1584-1589 ◽

Cited By ~ 144

Author(s):

Valerie B. O’Leary ◽

Christine M. Marchetti ◽

Raj K. Krishnan ◽

Bradley P. Stetzer ◽

Frank Gonzalez ◽

...

Keyword(s):

Insulin Resistance ◽

Oxygen Consumption ◽

Glucose Metabolism ◽

Exercise Training ◽

Visceral Fat ◽

Maximal Oxygen Consumption ◽

Subcutaneous Fat ◽

Abdominal Fat ◽

Fat Free Mass ◽

Men And Women

Exercise improves glucose metabolism and delays the onset and/or reverses insulin resistance in the elderly by an unknown mechanism. In the present study, we examined the effects of exercise training on glucose metabolism, abdominal adiposity, and adipocytokines in obese elderly. Sixteen obese men and women (age = 63 ± 1 yr, body mass index = 33.2 ± 1.4 kg/m2) participated in a 12-wk supervised exercise program (5 days/wk, 60 min/day, treadmill/cycle ergometry at 85% of heart rate maximum). Visceral fat (VF), subcutaneous fat, and total abdominal fat were measured by computed tomography. Fat mass and fat-free mass were assessed by hydrostatic weighing. An oral glucose tolerance test was used to determine changes in insulin resistance. Exercise training increased maximal oxygen consumption (21.3 ± 0.8 vs. 24.3 ± 1.0 ml·kg−1·min−1, P < 0.0001), decreased body weight ( P < 0.0001) and fat mass ( P < 0.001), while fat-free mass was not altered ( P > 0.05). VF (176 ± 20 vs. 136 ± 17 cm2, P < 0.0001), subcutaneous fat (351 ± 34 vs. 305 ± 28 cm2, P < 0.03), and total abdominal fat (525 ± 40 vs. 443 ± 34 cm2, P < 0.003) were reduced through training. Circulating leptin was lower ( P < 0.003) after training, but total adiponectin and tumor necrosis factor-α remained unchanged. Insulin resistance was reversed by exercise (40.1 ± 7.7 vs. 27.6 ± 5.6 units, P < 0.01) and correlated with changes in VF ( r = 0.66, P < 0.01) and maximal oxygen consumption ( r = −0.48, P < 0.05) but not adipocytokines. VF loss after aerobic exercise training improves glucose metabolism and is associated with the reversal of insulin resistance in older obese men and women.

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Relationship between visceral adiposity and intramyocellular lipid content in two rat models of insulin resistance

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00089.2004 ◽

2005 ◽

Vol 288 (1) ◽

pp. E106-E116 ◽

Cited By ~ 40

Author(s):

M. Korach-André ◽

J. Gao ◽

J. S. Gounarides ◽

R. Deacon ◽

A. Islam ◽

...

Keyword(s):

Insulin Resistance ◽

Fatty Acid ◽

Visceral Fat ◽

Visceral Adiposity ◽

Zucker Rats ◽

Intramyocellular Lipid ◽

Dexamethasone Treatment ◽

Fat Accumulation ◽

Visceral Fat Accumulation

High visceral adiposity and intramyocellular lipid levels (IMCL) are both associated with the development of type 2 diabetes. The relationship between visceral adiposity and IMCL levels was explored in diet- and glucocorticoid-induced models of insulin resistance. In the diet-induced model, lean and fa/fa Zucker rats were fed either normal or high-fat (HF) chow over 4 wk. Fat distribution, IMCL content in the tibialis anterior (TA) muscle (IMCLTA), and whole body insulin resistance were measured before and after the 4-wk period. The HF diet-induced increase in IMCLTA was strongly correlated with visceral fat accumulation and greater glucose intolerance in both groups. The increase in IMCLTA to visceral fat accumulation was threefold greater for fa/fa rats. In the glucocorticoid-induced model, insulin sensitivity was impaired with dexamethasone. In vivo adiposity and IMCLTA content measurements were combined with ex vivo analysis of plasma and muscle tissue. Dexamethasone treatment had minimal effects on visceral fat accumulation while increasing IMCLTA levels ∼30% ( P < 0.05) compared with controls. Dexamethasone increased plasma glucose by twofold and increased the saturated fatty acid content of plasma lipids [fatty acid (CH2) n/ωCH3 ratio +15%, P < 0.05]. The lipid composition of the TA muscle was unchanged by dexamethasone treatment, indicating that the relative increase in IMCLTA observed in vivo resulted from a decrease in lipid oxidation. Visceral adiposity may influence IMCL accumulation in the context of dietary manipulations; however, a “causal” relationship still remains to be determined. Dexamethasone-induced insulin resistance likely operates under a different mechanism, i.e., independently of visceral adiposity.

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Visceral Fat Accumulation Is Related to Impaired Pancreatic Blood Perfusion and Beta-Cell Dysfunction in Obese Women

Annals of Nutrition and Metabolism ◽

10.1159/000519251 ◽

2021 ◽

pp. 1-6

Author(s):

Radka Szotkowská ◽

Jan Gojda ◽

Andrea Plíhalová ◽

Jiří Weichet ◽

Jana Potočková ◽

...

Keyword(s):

Insulin Resistance ◽

Beta Cell ◽

Visceral Fat ◽

Blood Perfusion ◽

Beta Cell Dysfunction ◽

Fat Accumulation ◽

Visceral Fat Accumulation ◽

Cell Dysfunction ◽

Fasting Glycemia ◽

Pancreatic Perfusion

Aims/Hypothesis: Beta-cell failure plays a fundamental role in type 2 diabetes mellitus (T2DM) development. It has been shown that the beta-cells are among the most sensitive to hypoxia. We aimed to analyze whether decrease in pancreatic perfusion relates to 1/decline in beta-cell function and 2/visceral fat accumulation in patients with T2DM. Methods: Fifteen women with T2DM on metformin therapy alone and fifteen women of comparable age and BMI without prediabetes/diabetes were cross-sectionally examined: clinical and anthropometric examination, fast sampled intravenous glucose tolerance test (FSIVGTT), dynamic contrast-enhanced magnetic resonance imaging to assess pancreatic perfusion (area under the curve of postcontrast saturation, AUCTSIC), and visceral adiposity (VAT, calculated from transverse sections at the level L2–L5 vertebrae). Results: Pancreatic blood perfusion (AUCTSIC) did not differ between groups (p = 0.273), but it negatively correlated with BMI (r = −0.434, p = 0.017), WHR (r = −0.411, p = 0.024), and VAT (r = −0.436, p = 0.016) in both groups. Moreover, AUCTSIC in the head of the pancreas negatively correlated with the level of fasting glycemia (r = −0.401, p = 0.028) and HOMA-IR (r = −0.376, p = 0.041). Discussion/Conclusion: We showed that decreased pancreatic perfusion did not relate to beta-cell dysfunction in early stages of T2DM development, but it was related to VAT, insulin resistance, and higher fasting glycemia. Furthermore, lower pancreatic perfusion was related to VAT, insulin resistance, and higher fasting glycemia.

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Abstract 13081: Predictive Value of Visceral-to-subcutaneous Fat Ratio for Long-term Clinical Outcomes in Patients With Suspected Coronary Artery Disease

Circulation ◽

10.1161/circ.142.suppl_3.13081 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Keisuke Machida ◽

Kyuhachi Otagiri ◽

Tadashi Itagaki ◽

Takahiro Takeuchi ◽

Hiroshi Kitabayashi

Keyword(s):

Coronary Artery ◽

Visceral Fat ◽

Cardiovascular Events ◽

Subcutaneous Fat ◽

Coronary Risk Factors ◽

Long Term Outcomes ◽

Fat Accumulation ◽

Visceral Fat Accumulation ◽

Coronary Syndrome

Introduction: Although visceral fat accumulation is an important risk factor for coronary artery diseases (CAD), the relationship between visceral fat accumulation and its long-term outcomes has not been extensively investigated. Hypothesis: In patients with suspected CAD, the distribution of subcutaneous fat and visceral fat is associated with cardiovascular events. Methods: Computed tomography (CT) angiographies (CTA) were performed on 945 consecutive patients with suspected CAD. Plain abdominal CT scanning was performed to measure the patients’ visceral fat area (VFA) and subcutaneous fat area (SFA). The VFA/SFA (V/S) ratios were calculated to assess the visceral fat accumulation. Based on the results of the CTA, the prevalence of CAD was assessed. The patients were classified into low (<0.627), and high (≥0.627) V/S ratio groups, based on their median value, and the association between V/S ratio and long-term outcomes was evaluated. The primary endpoints were major cardiac adverse events (MACE), including all-cause death, new-onset acute coronary syndrome (ACS), emergent hospitalization due to cardiovascular disease, and any coronary revascularization. Results: The average follow-up period was 845.3 days. The baseline characteristics for patients in the high V/S ratio group were worse than those for patients in the low high V/S ratio group. As compared to the low V/S ratio group, a higher incidence of MACE and ACS, and a higher tendency of mortality was observed in the high V/S ratio group. After adjusting for traditional coronary risk factors, the V/S ratio was independently associated with incidence of MACE, ACS, and increase of mortality (table). Conclusions: The present study suggests that the V/S ratio is an independent predictor of long-term outcomes in patients with suspected CAD. The visceral fat accumulation indicated by high V/S ratio signifies a potential risk and may contribute to the future cardiovascular events in patients with suspected CAD.

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Fatty Liver Has Stronger Association With Insulin Resistance Than Visceral Fat Accumulation in Nonobese Japanese Men

Journal of the Endocrine Society ◽

10.1210/js.2019-00052 ◽

2019 ◽

Vol 3 (7) ◽

pp. 1409-1416 ◽

Cited By ~ 7

Author(s):

Satoshi Kadowaki ◽

Yoshifumi Tamura ◽

Yuki Someya ◽

Kageumi Takeno ◽

Hideyoshi Kaga ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Insulin Sensitivity ◽

Fatty Liver ◽

Visceral Fat ◽

Visceral Fat Area ◽

Japanese Men ◽

Fat Accumulation ◽

Visceral Fat Accumulation ◽

Intrahepatic Lipid

Abstract Context Asians have a high prevalence of insulin resistance, even in the nonobese state. Whereas both visceral fat accumulation (VFA) and fatty liver (FL) have been shown to be associated with insulin resistance, it is still unclear which is a better marker to predict insulin resistance in nonobese Asians. Objective The aim of this study was to investigate the relation between VFA or FL and insulin resistance in nondiabetic nonobese Japanese men who do not have diabetes. Design and Participants We studied 87 nonobese (body mass index <25 kg/m2) Japanese men without diabetes. Using a two-step hyperinsulinemic euglycemic clamp, we evaluated insulin sensitivity in adipose tissue, muscle, and liver. Intrahepatic lipid and abdominal visceral fat area were measured by 1H-magnetic resonance spectroscopy and MRI, respectively. Subjects were divided into four groups based on the presence or absence of VFA (visceral fat area ≥100 cm2) and FL (intrahepatic lipid ≥ 5%): control (non-VFA, non-FL; n = 54), VFA only (n = 18), FL only (n = 7), and VFA plus FL (n = 8). Results Subjects in the FL only and VFA plus FL groups had insulin resistance in adipose tissue and muscle, as well as relatively lower hepatic insulin sensitivity. The specific insulin sensitivities in these organs were comparable in the VFA only and control groups. Conclusions In nonobese Japanese men without diabetes, subjects with FL only or VFA plus FL but not VFA only had insulin resistance, suggesting that FL may be a more useful clinical marker than VFA to predict insulin resistance in nonobese Japanese men without diabetes.

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