Improved systemic metabolism and adipocyte biology in miR-150 knockout mice
Minsung Kang1, Xiaobing Liu1, Yuchang Fu1
1Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA.
Introduction:
Short non-coding micro-RNAs (miRNAs) are post-transcriptional factors that directly regulate protein expression by degrading or inhibiting target mRNAs; however, the role of miRNAs in obesity and cardiometabolic disease remains unclarified. Based on our earlier study demonstrating that miR-150 influences lipid metabolism, we have studied effects of miR-150 on systemic metabolism and adipocyte biology.
Materials And Methods:
Metabolic phenotypes including body weight, food intake, body composition, glucose tolerance and insulin sensitivity were assessed in WT and global miR-150 KO male mice fed a high-fat diet. Molecular changes in epididymal adipose tissue were evaluated through qRT-PCR and Western blotting.
Results:
miR-150 KO mice displayed lower body weight characterized by a reduction in % fat mass while % lean mass was increased. Lower body weight was associated with reduced food consumption and an increase in circulating leptin concentrations, as well as enhanced insulin sensitivity and glucose tolerance compared with WT mice. Absence of miR-150 resulted in increased mTOR expression known to participate in increased leptin production leading to reduction of food intake. Expression of PGC-1α, another target gene of miR-150, was also increased together with upregulation of PPARα and glycerol kinase in adipose tissue as well as other genes participating in triglyceride degradation and lipid oxidation.
Conclusion:
miR-150 KO mice showed metabolic benefits accompanied by reduced body weight, decreased energy intake, and enhanced lipid metabolism. miR-150 may represent both a biomarker and novel therapeutic target regarding obesity and insulin resistance.
Insights
MicroRNA-150 (miR-150) knockout mice exhibit reduced body weight, fat mass, and food intake, alongside improved insulin sensitivity and glucose tolerance. These findings suggest miR-150 is a potential therapeutic target for obesity and metabolic disorders.
Area of Science:
- Molecular Biology
- Metabolic Research
- Genetics
Background:
- MicroRNAs (miRNAs) are short non-coding RNAs regulating protein expression.
- The specific role of miRNAs in obesity and cardiometabolic diseases is not fully understood.
- Previous research indicated miR-150 influences lipid metabolism.
Purpose of the Study:
- To investigate the systemic metabolic effects of miR-150.
- To examine the impact of miR-150 on adipocyte biology.
- To determine if miR-150 plays a role in obesity and insulin resistance.
Main Methods:
- Assessed metabolic phenotypes (body weight, food intake, body composition, glucose tolerance, insulin sensitivity) in wild-type (WT) and miR-150 knockout (KO) male mice fed a high-fat diet.
- Analyzed molecular changes in epididymal adipose tissue using quantitative reverse transcription PCR (qRT-PCR) and Western blotting.
Main Results:
- miR-150 KO mice showed significantly lower body weight, reduced fat mass, and increased lean mass compared to WT mice.
- KO mice exhibited decreased food consumption, increased circulating leptin, and enhanced insulin sensitivity and glucose tolerance.
- Absence of miR-150 led to increased mTOR expression, PGC-1α, PPARα, and glycerol kinase, promoting triglyceride degradation and lipid oxidation.
Conclusions:
- miR-150 knockout mice demonstrated significant metabolic benefits, including reduced body weight, energy intake, and improved lipid metabolism.
- miR-150 emerges as a potential biomarker and a novel therapeutic target for managing obesity and insulin resistance.
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