Causes and Metabolic Consequences of Fatty Liver
Norbert Stefan, Konstantinos Kantartzis and Hans-Ulrich Häring



Type 2 diabetes and cardiovascular disease represent a serious threat to the health of the population worldwide. Although overall adiposity and particularly visceral adiposity are established risk factors for these diseases, in the recent years fatty liver emerged as an additional and independent factor. However, the pathophysiology of fat accumulation in the liver and the cross-talk of fatty liver with other tissues involved in metabolism in humans are not fully understood. Here we discuss the mechanisms involved in the pathogenesis of hepatic fat accumulation, particularly the roles of body fat distribution, nutrition, exercise, genetics, and gene-environment interaction. Furthermore, the effects of fatty liver on glucose and lipid metabolism, specifically via induction of subclinical inflammation and secretion of humoral factors, are highlighted. Finally, new aspects regarding the dissociation of fatty liver and insulin resistance are addressed.


I. Introduction

II. Prevalence and Diagnosis of Fatty Liver
A. Prevalence of fatty liver
B. Imaging techniques and histology
C. Laboratory and clinical findings


III. Causes of Fatty Liver
A. Body fat composition, hepatic lipid supply, and adipokines
B. Nutrition
C. Exercise and mitochondrial function
D. Genetics

IV. Metabolic Consequences of Fatty Liver
A. Dyslipidemia
B. Inflammation
C. Insulin resistance
D. Dissociation of fatty liver and insulin resistance

V. Concluding Remarks

Major determinants of fatty liver.

Metabolic consequences of fatty liver. Fat accumulation in the liver induces hyperglycemia, subclinical inflammation dyslipidemia, and the secretion of parameters that can be referred to as "hepatokines" (e.g., fetuin-A), thereby inducing insulin resistance, atherosclerosis, and possibly Beta-cell dysfunction and apoptosis. The degree of these conditions may be moderate [benign fatty liver (left panel)]. However, the same amount of hepatic fat accumulation may, by mechanisms that are yet not fully understood, be strongly associated with hepatic lipotoxicity, resulting in aggravation of hyperglycemia, subclinical inflammation, dyslipidemia, and an imbalance in hepatokine production as well as in their metabolic consequences. This state may be referred to as malign fatty liver (right panel).

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