Role of Fatty Acids in the Pathogenesis of Obesity and Fatty Liver: Impact of Bariatric Surgery

Abstract

Nonalcoholic fatty liver disease (NAFLD) spans a spectrum from simple steatosis to nonalcoholic steatohepatitis (NASH) to cirrhosis. Simple steatosis is the substrate upon which the more serious entities in the spectrum develop; it is the first ''hit'' in the multistep pathogenesis of NASH, which is considered the hepatic manifestation of the metabolic syndrome. Demonstration of the existence of regulatable fatty acid transport mechanisms has contributed to clarifying the role of fatty acid disposition in obesity, the various components of NAFLD, and the metabolic syndrome. Hepatic steatosis is closely linked to obesity. This linkage is based on the fact that obesity results in marked enlargement of the intraabdominal visceral fat depots. The eventual development of insulin resistance leads to continuous lipolysis within these depots, releasing fatty acids into the portal circulation, where they are rapidly translocated to the liver and reassembled into triglycerides. Reactive oxygen species, generated in the liver from oxidation of fatty acids, are precipitating factors in the cascade of events leading from simple steatosis to NASH. Dysregulation of fatty acid disposition, with ectopic lipid accumulation in other tissues, is a major contributing factor to other components of the metabolic syndrome. Bariatric surgery is an effective treatment for severe obesity, but its role in the management of the various forms of fatty liver disease is unclear. Our review of the literature that includes both initial and follow-up liver biopsies suggests that most obese patients with simple steatosis and NASH who undergo bariatric surgery will achieve improvement in hepatic histology, but that occasional patients, especially those who lose weight very rapidly, may show worsening of either fibrosis or steatohepatitis.

Downregulation of leptin and resistin expression in blood following bariatric surgery

“…corresponds with a decreased sensitivity to the hormone's effects [1,2]. Leptin may also have a role in the pathophysiology of obesity-related T2D.…”

Role of bariatric surgery in treatment of non-alcoholic fatty liver disease

“…105 Anemia due to iron, folic acid and vitamins B12, C and D (50-80% of BS patients) 106 deficiencies 107 and Iron deficiency which is common after gastric bypass. 108 There are many concerns that rapid weight loss, may have a role in worsening of NAFLD, 102,109 however Mathorin reported that in 95.7% of patients fibrosis score was not higher than 1. 110 To prevent the post operative effects and improve long-term outcomes of BS, it is obligatory to: 1.…”

Identification of cardiovascular genes in omentum from morbidly obese patients with type 2 diabetes

“…13,16 Moreover, during weight loss, lipolysis rapidly occurs from visceral adipose depots versus subcutaneous regions. 17 Thus, omental tissue may be particularly appropriate to examine in patients undergoing bariatric surgery as they lose significant amounts of weight after their procedure. Using microarray technology, this observational study compares the gene expression profiles of omental tissue from diabetic and non-diabetic morbidly obese patients undergoing bariatric surgery.…”