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United States Department of Agriculture

Agricultural Research Service

Research Project: NUTRITION, OBESITY, CARDIOVASCULAR HEALTH AND GENOMICS

Location: Human Nutrition Research Center on Aging

Title: Leptin receptor polymorphisms interact with polyunsaturated fatty acids to augment risk of insulin resistance and metabolic syndrome in adults

Authors
item Phillips, Ctherine -
item Goumidi, Louisa -
item Bertrais, Sandrine -
item Field, Martyn -
item Ordovas, Jose -
item Cupples, L. Adrienne -
item Defoort, Catherine -
item Lovegrove, Julia -
item Drevon, Christian -
item Blaak, Ellen -
item Gibney, Michael -
item Kiec-Wilk, Beata -
item Karlstrom, Britta -
item Lopez-Miranda, Jose -
item Mcmanus, Ross -
item Hercberg, Serge -
item Lairon, Denis -
item Planells, Richard -
item Roche, Helen -

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: November 23, 2009
Publication Date: February 1, 2010
Citation: Phillips, C.M., Goumidi, L., Bertrais, S., Field, M.R., Ordovas, J.M., Cupples, L., Defoort, C., Lovegrove, J.A., Drevon, C.A., Blaak, E.E., Gibney, M.J., Kiec-Wilk, B., Karlstrom, B., Lopez-Miranda, J., Mcmanus, R., Hercberg, S., Lairon, D., Planells, R., Roche, H.M. 2010. Leptin receptor polymorphisms interact with polyunsaturated fatty acids to augment risk of insulin resistance and metabolic syndrome in adults. Journal of Nutrition. 140(2):238-244.

Interpretive Summary: Leptin is a hormone that, in combination with its receptor, plays a key role in regulating energy intake and energy expenditure, including appetite and metabolism. It is one of the most important adipose derived hormones. The leptin receptor (LEPR) is associated with insulin resistance, a key feature of metabolic syndrome (MetS). The objective of this research was to investigate the relationship among LEPR polymorphisms, insulin resistance, and MetS risk and whether plasma fatty acids, a biomarker of dietary fatty acids, modulate this. LEPR polymorphisms and biomarkers were determined in 1754 subjects with and without MetS. One of the genetic polymorphisms examined was associated with MetS risk, insulin concentrations and insulin resistance. Low plasma (n-3) and high (n-6) PUFA status exacerbated the genetic risk conferred by this polymorphism to hyperinsulinemia and insulin resistance. Interestingly, these associations were abolished against a high (n-3) or low (n-6) PUFA background. Importantly, we replicated some of these findings in an independent cohort. These novel gene-nutrient interactions between LEPR and PUFA uncovers a group of people who are susceptible to diabetes but can avoid the disease by adopting diets high in n-3 and low in n-6 PUFA.

Technical Abstract: The leptin receptor (LEPR) is associated with insulin resistance, a key feature of metabolic syndrome (MetS). Gene-fatty acid interactions may affect MetS risk. The objective was to investigate the relationship among LEPR polymorphisms, insulin resistance, andMetSrisk and whether plasma fatty acids, a biomarker of dietary fatty acids, modulate this. LEPRpolymorphisms (rs10493380, rs1137100, rs1137101, rs12067936, rs1805096, rs2025805, rs3790419, rs3790433, rs6673324, and rs8179183), biochemical measurements, and plasma fatty acid profiles were determined in the LIPGENE-SU.VI.MAX study ofMetS cases and matched controls (n = 1754). LEPR rs3790433 GG homozygotes had increasedMetS risk compared with the minor A allele carriers [odds ratio (OR) = 1.65; 95% CI: 1.05–2.57; P = 0.028], which may be accounted for by their increased risk of elevated insulin concentrations (OR 2.40;95%CI: 1.28–4.50; P = 0.006) and insulin resistance (OR= 2.15; 95%CI: 1.18–3.90; P = 0.012). Low (less than median) plasma (n-3) and high (n-6) PUFA status exacerbated the genetic risk conferred by GG homozygosity to hyperinsulinemia (OR 2.92–2.94) and insulin resistance (OR 3.40–3.47). Interestingly, these associations were abolished against a high (n-3) or low (n-6) PUFA background. Importantly, we replicated some of these findings in an independent cohort. Homozygosity for the LEPRrs3790433 Gallele was associated with insulin resistance, which may predispose to increasedMetS risk. Novel gene-nutrient interactions between LEPR rs3790433 and PUFA suggest that these genetic influences were more evident in individuals with low plasma (n-3) or high plasma (n-6) PUFA.

Last Modified: 4/20/2014
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