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Published on: May 19, 2023
Adipose gene expression response of lean and obese mice to short-term dietary restriction
Evert M van Schothorst1, Jaap Keijer, Jeroen L A Pennings
1Laboratory of Toxicology, Pathology, and Genetics, National Institute of Public Health and the Environment, Bilthoven, The Netherlands. Evert.van.Schothorst@rivm.nl
Abstract:
Overweight and obesity lead to higher morbidity risks, which are alleviated even by mild weight loss. To gain insight in the molecular effects of weight loss in adipose tissue, we analyzed the effects of short-term dietary restriction (DR) on mice fed a low-fat diet (lean mice) or a high-fat diet (obese mice). Female C57Bl6/J mice on both diets were on DR until an average body weight loss of 20%, which was achieved in 8 to 12 days depending on body weight at the start of DR. Plasma free fatty acids and blood glucose levels decreased significantly on DR. In the (restricted) low-fat diet groups, gene expression analysis using adipose-enriched cDNA microarrays revealed only two transcripts to be significant differentially expressed by DR: up-regulation of malic enzyme (Mod1) and down-regulation of major urinary protein 1 (Mup1). Real-time polymerase chain reaction analysis confirmed these findings and showed, for the high-fat diet groups, an identical expression pattern for Mup1, whereas Mod1 showed an opposed gene expression pattern for the high-fat diet groups. In conclusion, initial weight loss induces transcriptional changes only in a very small number of adipose genes, which also depends on the (restricted) diet used.
Insights
Mild weight loss significantly impacts molecular pathways in adipose tissue. Dietary restriction alters gene expression differently in lean versus obese mice, affecting malic enzyme (Mod1) and major urinary protein 1 (Mup1).
Area of Science:
- Metabolism and Endocrinology
- Molecular Biology
- Obesity Research
Background:
- Overweight and obesity are linked to increased morbidity risks.
- Even minor weight reduction can mitigate these health risks.
- Understanding molecular changes in adipose tissue during weight loss is crucial.
Purpose of the Study:
- To investigate the molecular effects of short-term dietary restriction (DR) on adipose tissue.
- To compare these effects in lean mice on a low-fat diet versus obese mice on a high-fat diet.
Main Methods:
- Female C57Bl6/J mice on low-fat or high-fat diets underwent DR to achieve 20% body weight loss.
- Plasma free fatty acids and blood glucose levels were measured.
- Gene expression analysis in adipose tissue was performed using cDNA microarrays and real-time PCR.
Main Results:
- DR led to significant decreases in plasma free fatty acids and blood glucose.
- In low-fat diet groups, DR upregulated malic enzyme (Mod1) and downregulated major urinary protein 1 (Mup1).
- In high-fat diet groups, Mup1 showed similar downregulation, but Mod1 exhibited an opposing expression pattern.
Conclusions:
- Initial weight loss induces minimal transcriptional changes in adipose tissue.
- The specific diet influences the transcriptional response to weight loss.
- Mod1 and Mup1 are key genes affected by dietary restriction in adipose tissue, with diet-dependent variations.

