Burning hepatic fat: Therapeutic potential for liver-specific thyromimetics in the treatment of nonalcoholic fatty liver disease

Perspectives on cellular dysfunction in nonalcoholic steatohepatitis: a case of ‘multiorganelle failure’? Proceedings of a virtual workshop on nonalcoholic steatohepatitis

“…Taken together, these findings suggest that the pathogenesis of NASH is complex, with insulin resistance serving as an early, upstream factor in the subsequent inflammatory-fibrogenic cascade [29]. This is in full agreement with theories of pathogenesis based on experimental evidence (Figure 1) [30].…”

“…FFA: Free fatty acid; NAFLD: Nonalcoholic fatty liver disease; NASH: Nonalcoholic steatohepatitis; ROS: Reactive oxygen species. Reprinted from [30].…”

Leptin ameliorates insulin resistance and hepatic steatosis in Agpat2 lipodystrophic mice independent of hepatocyte leptin receptors

“…The reported relationship between plasma leptin and thyroid levels is inconsistent ( 56 ). Interestingly, a new class of selective thyromimetic drugs potently ameliorates liver triglycerides concentration in murine models of hepatic steatosis ( 57,58 ), suggesting that normalization of hypothyroxiemic state in Agpat2 Ϫ / Ϫ mice could be a relevant mechanism for leptin's benefi cial actions in the liver of these animals. The precise mechanisms of hypothyroxinemia in Agpat2 Ϫ / Ϫ mice remain unclear and may require further investigation.…”

Inflammation and fibrogenesis in steatohepatitis

“…Thus, excessive hepatocyte cell death and inadequate oval cell proliferation are thought to be involved in NASH fibrogenesis [15]. Figure 1 shows the current concept of steatohepatitis [16].…”