Hexarelin · research summary

The CD36-PPARγ Pathway in Metabolic Disorders.

International journal of molecular sciences · 2018. Summary drawn from the study's full text. Each statement is followed by the exact sentence it comes from. This is a research summary, not medical advice.

Study type

Review article summarizing recent advances in the GHRP-CD36-PPARγ pathway
“Recent advances on the emerging role of CD36 and GHRP hexarelin in regulating PPARγ downstream actions with benefits on atherosclerosis, hepatic cholesterol biosynthesis and fat mitochondrial biogenesis are summarized here.”

Subjects

Mice (apoE-null, PPARγ heterozygote, insulin-resistant), rats (GH-deficient, cachexia, atherosclerosis), and human cell lines (THP-1 macrophages)
“Using a vitamin-D3 induced rat model of atherosclerosis, hexarelin was shown to reduce foam cell formation, aortic calcium sedimentation, and vascular smooth muscle cell growth [105].”

Reported findings

Hexarelin reduces atherosclerotic lesion areas in apoE-null mice by activating the PPARγ-LXRα-ABC metabolic cascade to increase cholesterol efflux.
“In particular, GHRP EP80317, a CD36 specific ligand, and hexarelin were both potent in strongly reducing atherosclerotic lesion areas [100,101].”
Hexarelin promotes fatty acid oxidation and mitochondrial biogenesis in white adipose tissue, inducing a thermogenic profile similar to brown fat.
“Indeed, we found that hexarelin promoted beneficial effects in white adipose tissue, resulting in a striking thermogenic profile of FA oxidation and mitochondria biogenesis in cultured adipocytes and in epididymal fat of treated mice [113].”
Hexarelin represses de novo hepatic cholesterol synthesis by enhancing HMGR degradation and retaining SREBP-2 in the endoplasmic reticulum.
“We have recently reported that hexarelin regulates hepatic cholesterol homeostasis by repressing de novo cholesterol synthesis through enhanced 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) degradation and sterol regulatory element-binding protein (SREBP)-2 retention in the endoplasmic reticulum [82].”

Limitations stated by the authors

The molecular events by which CD36 and GHRPs exert their actions are not completely understood.
“While the molecular events by which CD36 and GHRPs exert their actions are not completely understood, increasing evidence supports a prominent role of scavenger receptor CD36 to initiate profound changes in key metabolic pathways, especially pertaining to PPARγ-controlled critical steps.”

Source: PubMed 29883404 · DOI 10.3390/ijms19051529 · all study summaries

Study type

Review article summarizing recent advances in the GHRP-CD36-PPARγ pathway

“Recent advances on the emerging role of CD36 and GHRP hexarelin in regulating PPARγ downstream actions with benefits on atherosclerosis, hepatic cholesterol biosynthesis and fat mitochondrial biogenesis are summarized here.”

Subjects

Mice (apoE-null, PPARγ heterozygote, insulin-resistant), rats (GH-deficient, cachexia, atherosclerosis), and human cell lines (THP-1 macrophages)

“Using a vitamin-D3 induced rat model of atherosclerosis, hexarelin was shown to reduce foam cell formation, aortic calcium sedimentation, and vascular smooth muscle cell growth [105].”

Reported findings

Hexarelin reduces atherosclerotic lesion areas in apoE-null mice by activating the PPARγ-LXRα-ABC metabolic cascade to increase cholesterol efflux.

“In particular, GHRP EP80317, a CD36 specific ligand, and hexarelin were both potent in strongly reducing atherosclerotic lesion areas [100,101].”

Hexarelin promotes fatty acid oxidation and mitochondrial biogenesis in white adipose tissue, inducing a thermogenic profile similar to brown fat.

“Indeed, we found that hexarelin promoted beneficial effects in white adipose tissue, resulting in a striking thermogenic profile of FA oxidation and mitochondria biogenesis in cultured adipocytes and in epididymal fat of treated mice [113].”

Hexarelin represses de novo hepatic cholesterol synthesis by enhancing HMGR degradation and retaining SREBP-2 in the endoplasmic reticulum.

“We have recently reported that hexarelin regulates hepatic cholesterol homeostasis by repressing de novo cholesterol synthesis through enhanced 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) degradation and sterol regulatory element-binding protein (SREBP)-2 retention in the endoplasmic reticulum [82].”

Limitations stated by the authors

The molecular events by which CD36 and GHRPs exert their actions are not completely understood.

“While the molecular events by which CD36 and GHRPs exert their actions are not completely understood, increasing evidence supports a prominent role of scavenger receptor CD36 to initiate profound changes in key metabolic pathways, especially pertaining to PPARγ-controlled critical steps.”