Research

Physiogenomic analysis of weight loss induced by dietary carbohydrate restriction

Gualberto Ruaño¹ , Andreas Windemuth¹ , Mohan Kocherla¹ , Theodore Holford² , Maria Luz Fernandez³ , Cassandra E Forsythe⁴ , Richard J Wood³ , William J Kraemer⁴ and Jeff S Volek⁴

¹Genomas, Inc., 67 Jefferson St, Hartford, CT 06106, USA

²Department of Biostatistics, Yale University School of Medicine, New Haven, CT 06520, USA

³Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, USA

⁴Human Performance Laboratory, Department of Kinesiology, University of Connecticut, Storrs, CT 06269, USA

author email corresponding author email

Nutrition & Metabolism 2006, 3:20doi:10.1186/1743-7075-3-20

Published:	15 May 2006

Abstract

Background

Diets that restrict carbohydrate (CHO) have proven to be a successful dietary treatment of obesity for many people, but the degree of weight loss varies across individuals. The extent to which genetic factors associate with the magnitude of weight loss induced by CHO restriction is unknown. We examined associations among polymorphisms in candidate genes and weight loss in order to understand the physiological factors influencing body weight responses to CHO restriction.

Methods

We screened for genetic associations with weight loss in 86 healthy adults who were instructed to restrict CHO to a level that induced a small level of ketosis (CHO ~10% of total energy). A total of 27 single nucleotide polymorphisms (SNPs) were selected from 15 candidate genes involved in fat digestion/metabolism, intracellular glucose metabolism, lipoprotein remodeling, and appetite regulation. Multiple linear regression was used to rank the SNPs according to probability of association, and the most significant associations were analyzed in greater detail.

Results

Mean weight loss was 6.4 kg. SNPs in the gastric lipase (LIPF), hepatic glycogen synthase (GYS2), cholesteryl ester transfer protein (CETP) and galanin (GAL) genes were significantly associated with weight loss.

Conclusion

A strong association between weight loss induced by dietary CHO restriction and variability in genes regulating fat digestion, hepatic glucose metabolism, intravascular lipoprotein remodeling, and appetite were detected. These discoveries could provide clues to important physiologic adaptations underlying the body mass response to CHO restriction.