Background: Diabetes mellitus (DM) is a chronic disorder that it is caused by the
absence of insulin secretion due to the inability of the pancreas to produce it (type 1 diabetes; T1DM),
or due to defects of insulin signaling in the peripheral tissues, resulting in insulin resistance
(type 2 diabetes; T2DM). Commonly, the occurrence of insulin resistance in T2DM patients reflects
the high prevalence of obesity and non-alcoholic fatty liver disease (NAFLD) in these individuals.
In fact, approximately 60% of T2DM patients are also diagnosed to have NAFLD, and this
condition is strongly linked with insulin resistance and obesity. NAFLD is the hepatic manifestation
of obesity and metabolic syndrome and includes a spectrum of pathological conditions, which
range from simple steatosis (NAFL), non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular
carcinoma. NAFLD manifestation is followed by a series of hepatic lipid deregulations and
the main abnormalities are increased triglyceride levels, increased hepatic production of VLDL and
a reduction in VLDL catabolism. During the progression of NAFLD, the production of ketone
bodies progressively reduces while hepatic glucose synthesis and output increases. In fact, most of
the fat that enters the liver can be disposed of through ketogenesis, preventing the development of
NAFLD and hyperglycemia.
Objective: This review will focus on the pathophysiological aspect of hepatic lipid metabolism
deregulation, ketogenesis, and its relevance in the progression of NAFLD and T2DM.
Conclusion: A better understanding of the molecular mediators involved in lipid synthesis and ketogenesis
can lead to new treatments for metabolic disorders in the liver, such as NAFLD.