Nuclear Hormone and Peptide Hormone Therapeutics for NAFLD This was published recently on ScienceDirect, this is a Journal-Pre proof waiting to be published. You have to Join to get full access.
"3.1 Growth Hormone Releasing Hormone
Growth hormone releasing hormone (GHRH) is an endocrine hormone produced in the hypothalamus
and works on its receptor (GHRH-R) in the anterior pituitary to stimulate the release of growth hormone
(GH). GH subsequently can engage hepatocytes to produce insulin-like growth factor-1 (IGF-1) and
induce lipolysis in adipocytes via promotion of hormone-sensitive lipase. The GHRH analog tesamorelin,
which is modified with a hexanoyl moiety at the N-terminus to improve proteolytic stability, has shown
benefit in HIV patients with lipodystrophy and GH-deficiency to reduce circulating triglycerides and
visceral adipose fat [106], as well as a decrease in serum levels of ALT [107].In HIV patients with NAFLD,
tesamorelin (2 mg daily) caused a greater reduction in relative hepatic fat fraction (37%) relative to
placebo (therapy group decreased by 32% whereas placebo group gained 5%) [108]. As expected, IGF-1
levels were increased and visceral adipose tissue was decreased, but circulating triglycerides trended to
be increased after 12 months of treatment. Analysis of biopsied livers demonstrate that tesamorelin
increased transcriptional markers of oxidative phosphorylation and decreased gene sets linked to
inflammation [109]. Whether these benefits on hepatic fat content translate to non-HIV patients remains to
be proven, but recent clinical results with GH in obese NAFL patients [110] lend credence to targeting this
biological pathway for NASH benefit. The recently announced phase 3 trial of tesamorelin in general
NASH patients will hopefully provide definitive proof. "
https://www.researchgate.net/publication/348344521_Pathophysiology_of_NASH_in_endocrine_diseases