Genetic and environmental factors have important role in the pathogenesis of obesity and metabolic diseases. We hypothesized that genes involved in energy intake, cellular lipid metabolism and pro-inflammatory adipokines influence obesity-related metabolic disturbances and food intake. We explored the association of GHRL (rs26311G > C and rs4684677A > T), PLIN1 (rs2289487G > A and rs894160G > A), RETN (rs3745367C > T and rs7408174G > A), and NAMPT (rs1319501T > C) variants with obesity, metabolic and inflammatory markers, and food intake composition. Clinical, anthropometric, and laboratory data were obtained from 237 adults. Genomic DNA was extracted and genetic variants were analyzed by real-time polymerase chain reaction. Food intake was assessed in 81 subjects with obesity, who underwent a 9-week nutritional orientation program. Multivariate logistic regression analysis adjusted by covariates showed association of GHRL rs26311-G and rs4684677-A alleles with risk of type 2 diabetes (T2D) and/or metabolic syndrome ( P < .05), and RETN rs7408174-C allele with risk of T2D and obesity ( P < .05). Covariate-adjusted multivariate linear regression analysis showed association of PLIN1 rs894160-G allele with increased waist-to-hip ratio ( P = .003). The nutritional orientation program reduced carbohydrate and total fat intake, in subjects with obesity ( P < .05). Analysis of basal data revealed associations of PLIN1 rs894160-G with increased body mass index, PLIN1 rs2289487-A with reduced intake of total fat, monosaturated fatty acids and cholesterol, and RETN rs3745367A with increased intake of protein and saturated fatty acids ( P < .05). GHRL rs26311-G was associated with increased postprogram protein intake ( P = .044). In conclusion, variants in GHRL, RETN, and PLIN1 are associated with obesity, T2D, metabolic syndrome, and increased waist-to-hip ratio, and influence food consumption in adults with obesity.<br /> (c) 2024 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.