Can We Harness Our Genes to Burn More Calories?

Newswise — NEW ORLEANS, LA: Researchers say they have identified a potential pathway in our muscle tissue to improve the rate at which our bodies burn calories. The study is one of the first to explore the tie between genetics and calorie burn (or energy expenditure), a relatively new area of biological study. The findings of the study were unveiled during a poster presentation at The Obesity Society Annual Meeting at ObesityWeek 2016 in New Orleans.

“Obesity research continues to show that our ability to gain or lose weight may not be completely reliant on individual behaviors, but perhaps our genetic traits,” says lead author Paolo Piaggi, PhD, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health. “This new study is one of the first to identify a specific genetic pathway in our muscle tissue that we may be able to harness to develop new treatments for obesity.”

To reach their findings, researchers at NIDDK’s Phoenix Epidemiology and Clinical Research Branch performed an exome-wide gene expression study in skeletal muscle biopsies from 219 healthy individual donors at rest and over 24 hours and measured long-term weight change over seven years. Among the genes associated with energy expenditure (EE), they found that the expression of the THNSL2 gene in skeletal muscle tissue had the strongest association between lower energy expenditure and weight gain. Based on their findings, it appears that an mRNA splice variant, a key player in translating a gene to a protein, impacts the production of a cytokine (SOFAT) secreted by T-cells that stimulates production of interleukin 6, suggesting that SOFAT may influence EE through the inflammatory pathways related to EE and obesity.

“The research brings us one step closer to better understanding the variation in weight gain among individuals, particularly when on similar diets,” said Anthony Comuzzie, PhD, spokesperson for The Obesity Society and Scientist at Texas Biomedical Research Institute. “We know that there are ties between our genes and energy expenditure, and this study offers several potentially important extensions to that work, in particular by implicating a specific pathway for treatment.”

Abstract and author contact information are available below.

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Funding for this research was provided by the NIH Intramural Research Program. The content of this announcement is the sole responsibility of the authors and does not necessarily represent the official views or imply endorsement of the NIH.

Outside ExpertAnthony Comuzzie, PhD, spokesperson for The Obesity Society and Scientist at Texas Biomedical Research InstituteContact: [email protected]

AuthorPaolo Piaggi, PhD, National Institute of Diabetes and Digestive and Kidney Diseases

AbstractGenome-wide Gene Expression Study in Skeletal Muscle to Identify Genes Associated with Energy Expenditure and Weight Gain

Background A relatively lower energy expenditure (EE) predicts long-term weight gain. As both EE and body weight are heritable traits, it is possible that inter-individual differences in gene expression level ascribable to genetic regulatory variations may influence EE, thereby predisposing some individuals to weight gain. We aimed to identify differentially expressed genes implicated in the pathogenesis of human obesity via an effect on EE.

MethodsSkeletal muscle biopsies from 219 healthy Pima Indians (150 men, age: 29±7 yr; body fat 32±8%) were analyzed by the Affymetrix Human Exon 1.0 ST array. Most subjects had measures of 24h EE assessed in a whole-room indirect calorimeter during energy balance (n=126), resting EE by ventilated hood system (REE, n=138), and long-term weight change (n=170, median follow-up time: 7 yrs, range: 1-16). Expression levels of 16,861 autosomal genes were batch- and sex- standardized and analyzed for association with EE measures after adjustment for age, sex, body composition and heritage.

ResultsNo transcript achieved transcriptome-wide statistical significance (p<3x10−6 via Bonferroni correction) with 24h EE or REE, where 133 and 77 transcripts were associated at p<0.01, respectively. THNSL2 was one of the strongest associations, with increased expression being associated with both a lower 24hEE (β=−46 kcal/day per SD increase, p=10-3) and a lower REE (β=−47 kcal/day, p=8x10-3), while also being associated with weight gain (r=+0.19, p=10-2). THNSL2 is bimodally expressed, and an mRNA splice variant of THNSL2 encodes the osteoclastogenic factor of activated T cells (SOFAT), a cytokine secreted by T-cells that stimulates production of interleukin 6. IL-6-deficient mice develop obesity by reduced EE.

ConclusionsIncreased expression of THNSL2 in human skeletal muscle is associated with lower EE and predicts weight gain. The encoded splice variant osteoclastogenic factor may explain this relationship via its role in inflammatory pathways related to EE and obesity.

CitationPiaggi P. National Institute of Diabetes and Digestive and Kidney Diseases. Poster abstract presentation at: The Obesity Society Annual Meeting at ObesityWeekSM 2016; October 31 – November 4, 2016. http://www.obesityweek.com.

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