Misregulation of PPAR Functioning and Its Pathogenic Consequences Associated with Nonalcoholic Fatty Liver Disease in Human Obesity

作者：Videla Luis A^*; Pettinelli Paulina

来源：PPAR Research, 2012, 2012: 107434.

DOI：10.1155/2012/107434

Nonalcoholic fatty liver disease in human obesity is characterized by the multifactorial nature of the underlying pathogenic mechanisms, which include misregulation of PPARs signaling. Liver PPAR-alpha downregulation with parallel PPAR-gamma and SREBP-1c up-regulation may trigger major metabolic disturbances between de novo lipogenesis and fatty acid oxidation favouring the former, in association with the onset of steatosis in obesity-induced oxidative stress and related long-chain polyunsaturated fatty acid n-3 (LCPUFA n-3) depletion, insulin resistance, hypoadiponectinemia, and endoplasmic reticulum stress. Considering that antisteatotic strategies targeting PPAR-alpha revealed that fibrates have poor effectiveness, thiazolidinediones have weight gain limitations, and dual PPAR-alpha/gamma agonists have safety concerns, supplementation with LCPUFA n-3 appears as a promising alternative, which achieves both significant reduction in liver steatosis scores and a positive anti-inflammatory outcome. This latter aspect is of importance as PPAR-alpha downregulation associated with LCPUFA n-3 depletion may play a role in increasing the DNA binding capacity of proinflammatory factors, NF-kappa B and AP-1, thus constituting one of the major mechanisms for the progression of steatosis to steatohepatitis.

• 出版日期2012