Opioid receptor mu 1 gene, fat intake and obesity in adolescence

Abstract

Dietary preference for fat may increase risk for obesity. It is a complex behavior regulated in part by the amygdala, a brain structure involved in reward processing and food behavior, and modulated by genetic factors. Here, we conducted a genome-wide association study (GWAS) to search for gene loci associated with dietary intake of fat, and we tested whether these loci are also associated with adiposity and amygdala volume. We studied 598 adolescents (12-18 years) recruited from the French-Canadian founder population and genotyped them with 530 011 single-nucleotide polymorphisms. Fat intake was assessed with a 24-hour food recall. Adiposity was examined with anthropometry and bioimpedance. Amygdala volume was measured by magnetic resonance imaging. GWAS identified a locus of fat intake in the μ-opioid receptor gene (OPRM1, rs2281617, P=5.2 × 10(-6)), which encodes a receptor expressed in the brain-reward system and shown previously to modulate fat preference in animals. The minor OPRM1 allele appeared to have a 'protective' effect: it was associated with lower fat intake (by 4%) and lower body-fat mass (by ∼2 kg, P=0.02). Consistent with the possible amygdala-mediated inhibition of fat preference, this allele was additionally associated with higher amygdala volume (by 69 mm(3), P=0.02) and, in the carriers of this allele, amygdala volume correlated inversely with fat intake (P=0.02). Finally, OPRM1 was associated with fat intake in an independent sample of 490 young adults. In summary, OPRM1 may modulate dietary intake of fat and hence risk for obesity, and this effect may be modulated by subtle variations in the amygdala volume.

Prenatal exposure to cigarette smoke interacts with OPRM1 to modulate dietary preference for fat

“…13 Prenatal exposure to maternal cigarette smoking is a well-established risk factor for obesity in the exposed offspring [17][18][19] and has been associated with enhanced dietary preference for fat.…”

“…[6][7][8] Preference for fatty foods is a complex trait regulated by genetic and environmental factors, but only a few such factors have been identified in human populations. [9][10][11][12][13][14] These include the opioid receptor mu-1 gene (OPRM1) 13 and prenatal exposure to maternal cigarette smoking (PEMCS).…”

Opioidergic and dopaminergic modulation of cost/benefit decision-making in Long Evans Rats

“…In line with the clinical literature, our studies indicate a role for DA and EOS mechanisms in regulating the motivation to work for and consume foods. Dysregulation to these systems might produce the compulsive-like patterns of food consumption and impaired decision-making seen during disorders like bulimia nervosa and binge eating disorder [70][71][72][73][74]; they may be responsible for generating increased hedonic responses derived from consuming palatable foods, the development of obsessive desires/cravings to consume foods, or both.…”

Effect of opioid receptors agonists on feeding behaviour using different diets in ad libitum fed neonatal chicken

“…Preference for fat is a complex feeding behaviour regulated by reward-related mechanisms to maintain energy balance and expenditure (Haghighi et al 2014). Based on the literature review, there is no report on the role of opioidergic receptors in appetite regulation in response to different diet types in avian.…”

“…This phenomenon is linked to reward behaviour which caused its complex process (Haghighi et al 2014). Despite considerable progress being made in characterizing the mechanisms and neural pathways underlying opioid-induced feeding behaviour, the role of the opioidergic system in determining macronutrient preference remains unclear (Taha 2010).…”