November 02, 2016
2 min read

Increased gene expression may predict weight gain

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NEW ORLEANS — Weight gain may be predicted and energy expenditure may be lower with increased expression of the THNSL2 gene in human skeletal muscle, according to findings presented here.

“Obesity arises from a chronic imbalance between energy intake — the food we eat — and energy expenditure — the energy our body uses,” Paolo Piaggi, PhD, of National Institute of Diabetes and Digestive Kidney Diseases at the National Institutes of Health, told Endocrine Today. “As lower [energy expenditure] plays a role in long-term weight gain, and given that both obesity and [energy expenditure] are in part genetically determined, we sought to identify genes that influence body weight change via an effect on [energy expenditure] in muscle tissue.”

Piaggi and colleagues evaluated skeletal muscle biopsies from 219 healthy Pima Indians (150 men; mean age, 29 years; mean body fat, 32%) to identify differentially expressed genes implicated in the pathogenesis of human obesity by an effect on energy expenditure.

The Affymetrix Human Exon 1.0 ST array was used to analyze the skeletal muscle biopsies. A whole-room indirect calorimeter during energy balance was used to measure 24-hour energy expenditure in 126 participants; ventilated hood system was used to measure resting energy expenditure in 138 participants and long-term weight change (median follow-up time, 7 years) was measured in 170 participants.

After adjustment for age, sex, body composition and heritage, expression levels of 16,861 autosomal genes were batch- and sex-standardized and analyzed for relationships with energy expenditure measures.

Transcriptome-wide statistical significance was not achieved by any transcript (P < 3x10-6 viz Bonferroni correction) with 24-hour energy expenditure or resting energy expenditure. The strongest association was found with THNSL2, and its increased expression was related to a lower 24-hour energy expenditure (P = 10-3), lower resting energy expenditure (P = 8x10-3) and weight gain (P = 10-2).
“This study aimed to identify genes expressed in skeletal muscle, which are involved in human metabolism and predict long-term weight change,” Piaggi told Endocrine Today. “We found that higher levels of expression for the THNSL2 gene are associated with reduced energy expenditure — both at rest and during 24 hours. Also, higher expression levels of THNSL2 are associated with higher rates of weight gain over time. As this is a preliminary study to identify novel genes potentially affecting the metabolic pathways involved in the etiology of obesity, clinical implications are limited at present. However, as an isoform of the THNSL2 gene interacts with interleukin 6 in mouse models, it may be that future interventions aimed to alter the inflammatory pathways related to cytokines response could constitute a potential target for obesity treatment.” – by Amber Cox


Piaggi P, et al. Poster T-P-3243-DT. Presented at: ObesityWeek; Oct. 31-Nov. 4, 2016; New Orleans.

Disclosure: Piaggi reports no relevant financial disclosures.