Metrnl increases blood HDL-cholesterol and decreases blood triglyceride

OBJECTIVE Dyslipidemias are risk factors for both cardiovascular diseases and type 2 diabetes.Many adipose-derived proteins/adipokines participate in modulation of blood lipids. As a new identified adipokine,metrnlin adipose is involved in regulation of blood triglyceride, suggesting metrnl may play extensive roles in regulation of blood lipid. However, the exact effects and the underling mechanisms of Metrnl on regulation of blood lipid remain unexplored. METHODS Metrnl global knockout mice were generated and fed with normal chow diet or high fat diet. Major clinical lipid parameters including blood triglyceride(TG), total cholesterol(TC), high density lipoprotein(HDL) cholesterol, low density lipoprotein(LDL) cholesterol, and non-esterified fatty acid(NEFA)were detected with automatic biochemistry analyzer. Further,intestine and liver specific knockout mice were generated and the major clinical lipid parameters were detected to clarify which tissue contributes to metrnl regulated alterations of clinical lipid parameters. RESULTS Global knockout of metrnl had no effects on clinical parameters under normal chow diet, but increased blood triglyceride by 14%,which was consistent with our previous findings in metrnl adipose specific knockout mice, and decreased total cholesterol by 16% and HDL-cholesterol by 24% under high fat diet. Intestine specific knockout of metrnl failed to alter any of the clinical lipid parameters under both normal chow diet and high fat diet. Notably, liver specific knockout of metrnl downregulated HDL-cholesterol by 24%, TC by20% and LDL-cholesterol by 16% without alterations of blood TG and NEFA under high fat diet. CONCLUSION Global deficiency of metrnl downregulates blood HDLcholesterol and upregulates blood TG, and liver participates in the former and adipose tissue the latter.