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Mechanisms of Disease: adipocytokines and visceral adipose tissue—emerging role in nonalcoholic fatty liver disease

Nature Clinical Practice Gastroenterology & Hepatology volume 2, pages 273–280 (2005)Cite this article

Abstract

There is increasing evidence that visceral adipose tissue is a causative risk factor for fatty liver and nonalcoholic steatohepatitis. Adipose tissue-derived secretory proteins are collectively named adipocytokines. Obesity and mainly visceral fat accumulation impair adipocyte function and adipocytokine secretion and the altered release of these proteins contributes to hypertension, impaired fibrinolysis and insulin resistance. This review summarizes recent findings on the role of the adipocytokines adiponectin, leptin and resistin in the context of hepatic insulin resistance, fatty liver and liver fibrosis. Elevated levels of resistin antagonize hepatic insulin action and raise plasma glucose levels. Leptin exerts insulin-sensitizing effects, but obesity has been linked to leptin resistance and low levels of circulating leptin receptor, indicating that high levels of leptin cannot mediate its beneficial effects. Adiponectin improves insulin sensitivity; however, low circulating adiponectin is found in the obese state. Adiponectin is an anti-inflammatory protein, whereas leptin augments inflammation and fibrogenesis. Disturbed adipocytokine secretion might, therefore, promote hepatic steatosis and the development of nonalcoholic steatohepatitis. The beneficial effects of the therapeutic approaches so far tested in the treatment of fatty liver disease and fibrosis might be due to the modulation of these adipocytokines.

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Figure 1: Histological photograph (×400) of a liver biopsy of a patient with nonalcoholic steatohepatitis.
Figure 2: Visceral adipose tissue and fatty liver disease.
Figure 3: Visceral fat and nonalcoholic fatty liver disease: cross-talk between visceral adipose tissue and the liver.

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Acknowledgements

Figure 1 is a gift from Dr Frauke Bataille, whose generosity is highly appreciated.

Author information

Authors and Affiliations

  1. doctor Department of Internal Medicine I, University of Regensburg, Germany

    Andreas Schäffler

  2. Director Department of Internal Medicine I, University of Regensburg, Germany

    Jürgen Schölmerich

  3. molecular biologist in the Department of Internal Medicine I, University of Regensburg, Germany

    Christa Büchler

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  1. Andreas Schäffler
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  2. Jürgen Schölmerich
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  3. Christa Büchler
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Correspondence to Christa Büchler.

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Glossary

GLITAZONES

Insulin-sensitizing drugs such as pioglitazone or rosiglitazone that are used for the treatment of type 2 diabetes mellitus

ADIPONECTIN

An anti-inflammatory and adipocyte-specific secretory protein, the levels of which decrease in the context of obesity-related insulin resistance

KK-Ay OBESE MICE

The Ay mutation was introduced onto the KK strain background; mice of the KK strain develop diabetes of polygenic origin; Ay heterozygotes usually become obese and infertile within a few months after birth

LEPTIN

The satiety hormone; leptin is mainly produced and secreted by mature adipocytes and acts mostly in the hypothalamus by decreasing neuropeptide Y synthesis and release

RESISTIN

A protein produced during adipocyte differentiation, resistin is possibly linked to hepatic insulin resistance by interfering with hepatic gluconeogenesis

METFORMIN

A biguanide hypoglycemic agent used in the treatment of type 2 diabetes mellitus for improving glycemic control

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Schäffler, A., Schölmerich, J. & Büchler, C. Mechanisms of Disease: adipocytokines and visceral adipose tissue—emerging role in nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol 2, 273–280 (2005). https://doi.org/10.1038/ncpgasthep0186

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