Visceral Fat: Culprit or Canary?

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Key points

  • Excess free fatty acid (FFA) release from adipose tissue can cause tissue dysfunction/insulin resistance.

  • Most systemic FFA comes from upper-body subcutaneous fat.

  • Visceral fat FFA release may disproportionately affect the liver.

  • Visceral fat gain is associated with dysfunctional subcutaneous adipose function, not the cause of it.

  • Adipocyte hypertrophy appears to be the common denominator for dysfunctional adipose tissue.

Anatomy of visceral and subcutaneous fat: structure and functions

Each of the major fat depots has unique characteristics. Upper-body subcutaneous fat includes superficial and deep truncal depots,11,12 upper-extremity fat, and, in women, breast adipose tissue. Upper-body subcutaneous fat is usually the largest depot. For purposes of simplicity, lower-body subcutaneous fat can be summed to include gluteal, femoral, and calf adipose tissue, although there is evidence that gluteal fat and thigh fat are somewhat different.13 The lower-body fat depot is commonly

Associations between visceral fat and metabolic health

As noted above, visceral fat is a stronger predictor of insulin resistance–related illnesses than is body mass index. Increased visceral fat is associated with glucose intolerance,26 and insulin sensitivity correlates with visceral fat mass in normal adults27,28 and in people with type 2 diabetes.29,30 There is also a strong correlation between visceral fat and circulating very-low-density lipoprotein (VLDL) triglyceride concentrations,26 which may relate to greater delivery of FFA to the liver

What is known about visceral adipose tissue: fat storage, lipolysis, and adipokines?

Studies of visceral adipocytes using in vitro techniques are numerous. However, extrapolating from in vitro studies to in vivo physiology is challenging. The data generated from such studies often examine parameters such as maximum rates of lipolysis (which seldom occurs in vivo), messenger RNA content, protein content, or enzyme activities as surrogates for in vivo function. In addition, data are frequently expressed relative to cell number with little consideration for how cell number/size

Free fatty acid effects on tissue function

Although the delivery of FFA from adipose tissue into the circulation to provide fuel for lean tissue is vital for normal tissue function, there is ample evidence that excess FFA induces insulin resistance in humans44, 45, 46 by interfering with insulin signaling.47 Furthermore, short-term suppression of lipolysis with Acipimox in obese humans improves the suppression of hepatic glucose production48 and stimulates muscle glucose uptake.49 In animal models, it is possible to manipulate lipolysis

Association between visceral fat and dysregulation of subcutaneous adipose dysfunction

Dr Danforth most clearly stated the hypothesis that abnormalities of subcutaneous fat were at the heart of the visceral obesity/insulin resistance/type 2 diabetes phenomenon in 2000.54 He posited that the hypertrophic nature of abdominal subcutaneous adipocytes in those predisposed to type 2 diabetes could be explained by a failure of preadipocytes to differentiate in response to the need for additional body fat expansion. Hypertrophic adipocytes have excess rates of lipolysis and are insulin

Summary

Although there is no question that excess amounts of visceral fat are strongly associated with several metabolic abnormalities, only a subset of these are likely to be a direct result of dysfunction of visceral fat. These abnormalities include hypertriglyceridemia, increases in CRP, and possibly hepatic insulin resistance with regards to suppression of glucose production. The most likely cause of excess visceral fat gain seems to be the forced storage of fatty acids, possibly from excess

Disclosure

This work was supported by National Institutes of Health Grants DK45343 and DK40484. The content is solely the responsibility of the author and does not necessarily represent the official views of the National Institutes of Health.

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