Hepatic lipid accumulation: cause and consequence of dysregulated glucoregulatory hormones

摘要: Fatty liver can be diet, endocrine, drug, virus or genetically induced. Independent of cause, hepatic lipid accumulation promotes systemic metabolic dysfunction. By acting as peroxisome proliferator-activated receptor (PPAR) ligands, non-esterified fatty acids upregulate expression gluconeogenic, beta-oxidative, lipogenic and ketogenic genes, promoting hyperglycemia, hyperlipidemia ketosis. The typical hormonal environment in disease consists hyperinsulinemia, hyperglucagonemia, hypercortisolemia, growth hormone deficiency elevated sympathetic tone. These endocrine changes further encourage steatosis by regulating adipose tissue lipolysis, uptake, de novo lipogenesis (DNL), beta-oxidation, ketogenesis export. Hepatic may induced 4 separate mechanisms: (1) increased uptake circulating acids, (2) acid synthesis, (3) decreased beta-oxidation (4) This review will discuss the regulation each mechanism comparing multiple physiological models accumulation. Nonalcoholic (NAFLD) is typified oxidation Chronic signaling through PPARgamma results gene that allow concurrent activity DNL beta-oxidation. importance driving dysfunction highlighted common disturbances across many conditions result liver. Understanding mechanisms underlying develops a consequence critical to identifying points intervention this increasingly prevalent state.