Adiponectin and alcoholic fatty liver disease

Abstract

Worldwide, one of the most prevalent forms of chronic disease is alcoholic fatty liver, which may progress to more severe forms of liver injury including steatohepatitis, fibrosis, and cirrhosis. The molecular mechanisms by which ethanol consumption causes accumulation of hepatic lipid are multiple and complex. Chronic ethanol exposure is thought to cause enhanced hepatic lipogenesis and impaired fatty acid oxidation by inhibiting key hepatic transcriptional regulators such as AMP‐activated kinase (AMPK), sirtuin 1 (SIRT1), PPAR‐gamma coactivator alpha (PGC‐1α), peroxisome proliferator‐activated receptor alpha (PPARα), and sterol regulatory element‐binding protein 1 (SREBP‐1). Adiponectin is an adipose‐derived hormone with a variety of beneficial biological functions. Increasing evidence suggests that altered adiponectin production in adipose tissue and impaired expression of hepatic adiponectin receptors (AdipoRs) are associated with the development of alcoholic liver steatosis in several rodent models. More importantly, studies have demonstrated a protective role of adiponectin against alcoholic liver steatosis. The hepato‐protective effect of adiponectin is largely mediated by the coordination of multiple signaling pathways in the liver, leading to enhanced fat oxidation, reduced lipid synthesis and prevention of hepatic steatosis. This review begins with an assessment of the current understanding of the role of adiponectin and its receptors in the regulation of lipid homeostasis in liver, with emphasis on their relationship to the development of alcoholic liver steatosis. Following sections will review hepatic signaling molecules involved in the protective actions of adiponectin against alcoholic fatty liver and summarize the current knowledge of regulatory mechanisms of adiponectin expression and secretion in response to chronic ethanol exposure. We will conclude with a discussion of potential strategies for treating human alcoholic fatty liver disease (AFLD), including nutritional and pharmacological modulation of adiponectin and its receptors. © 2008 IUBMB IUBMB Life, 60(12): 790–797, 2008

C/EBP beta and C/EBP delta expression is elevated in the early phase of ethanol-induced hepatosteatosis in mice

“…Thus, alcohol consumption can lead to the development of hepatic steatosis. Most studies on alcoholic hepatic steatosis have focused on the ability of ethanol to shift the redox state in the liver and to inhibit fatty acid oxidation [3,4] . Indeed, previous studies have shown the repression of some enzymes involved in fatty acid oxidation and induction of lipogenic enzymes in ethanol-fed animals [2,5] .…”

Activation of peroxisome proliferator-activated receptor-γ by rosiglitazone improves lipid homeostasis at the adipose tissue-liver axis in ethanol-fed mice

“…All these alcohol effects on hepatic lipid metabolism favor lipid accumulation in the liver. Furthermore, extrahepatic factors such as adipokines secreted from the white adipose tissue (WAT) critically regulate hepatic lipid homeostasis (34,36,48). Previous studies have demonstrated that alcohol consumption causes WAT dysfunction, which impacts hepatic lipid homeostasis via an organ-organ interaction mechanism (36,48).…”

“…Adiponectin is one of the most important adipokines and regulates hepatic lipid metabolism toward reduction of lipid content in the liver (34,36,48). Adiponectin signaling in the liver leads to activation of AMPK (5=-adenosine monophosphate-activated protein kinase) pathway via AdipoR1/2 (adiponectin receptor 1/2).…”

Profiles of Liver Function Tests among Type 2 Diabetic Patients Who are Receiving Different Anti-Diabetic Drugs Attending Tikur Anbessa Specialized Hospitals

“…The study population consisted of 70 type 2 diabetic patients who are receiving different anti-diabetic drugs and 35 diabetic patients who did not started any medication. Hence a total of 105 diabetic patients were considered in the study [37][38][39][40][41][42][43][44][45][46][47][48][49][50].…”