MedWire News: A peroxisome proliferator-activated receptor gene (PPAR)γ2 variant previously shown to reduce the risk for weight gain and insulin resistance in mice eating a low-fat diet has the opposite effect in mice that are given a high-fat diet, study findings show.
The Pro12Ala variant of PPARγ2 moderately decreases the activity of PPARγ2, which is commonly found in adipose tissues and promotes a “thrifty” phenotype.
“The Ala12 allele has also been associated with reduced weight gain and improved insulin sensitivity, particularly in lean subjects; however, these observations have been challenged, especially in obese subjects where the Ala allele has been associated with increased weight gain,” note Johan Auwerx (Louis Pasteur University, Illkirch, France) and co-workers.
“Thus, the Pro12Ala genotype may be sensitive to environmental influence, such that the Ala allele is beneficial in lean subjects but could be detrimental when coexisting with obesity,” the authors write.
To test this idea, Auwerx and team studied mice with an extra copy of the Pro12Ala allele. When these mice were given a normal diet their fat mass decreased by an average of 35% compared with mice that lacked the allele.
Conversely, when mice with two copies of Pro12Ala were given a high-fat diet they gained significantly more weight than mice that lacked the variant, with body mass indices of 48 versus 40 kg/m2 after 16 weeks, respectively.
“Collectively, our results establish the diet-dependent influence of the PPARγ2 Pro12Ala variant on metabolic control via modulated cofactor interaction and changes in gene expression patterns in mice,” summarize the authors.
“These data hence consolidate PPARγ2 as an important factor at the interface between genes and the environment and may provide avenues to better treatment strategies for insulin resistance in Type 2 diabetes and the metabolic syndrome,” the researchers conclude in the journal Cell Metabolism.
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