Background: Evidence suggests that the beneficial effects of weight-loss diet interventions on improvement in cardiovascular risk factors may be partly through modulating secretion of adiponectin from adipose tissue. However, it remains unclear whether the long-term weight-loss diets change adiponectin levels; and how such changes, if exist, affect cardiometabolic risk.
Objectives: To investigate effects of weight-loss diets with different compositions of macronutrients on long-term changes of circulating adiponectin concentrations and cardiometabolic risk factors, as well as dietary interactions with variation in the adiponectin gene.
Methods: In the 2-year Preventing Overweight Using Novel Dietary Strategies (POUNDS Lost) trial, 811 overweight or obese adults were randomly assigned to 1 of 4 diets; the targeted percentages of energy derived from fat, protein, and carbohydrates in the 4 diets were 20, 15, and 65%; 20, 25, and 55%; 40, 15, and 45%; and 40, 25, and 35%. The current analysis was restricted to participants who had baseline plasma adiponectin measurement (n=768). Circulating adiponectin and cardiometabolic outcomes were repeatedly measured at baseline, 6 months, and 2 years. We genotyped single-nucleotide polymorphism rs266171 in the adiponectin gene. Linear mixed models were used to compare changes in adiponectin concentrations across diet groups over the intervention and predict trajectory of changes in cardiometabolic risk factors.
Results: Circulating adiponectin concentrations significantly increased over 2 years, similarly in 4 weight-loss diet intervention groups. Change of plasma adiponectin was significantly associated with decreases in weight, waist circumference, triglycerides, fasting insulin, and insulin resistance measured by homeostasis model assessment of insulin resistance (HOMA-IR), and increase in HDL cholesterol, after adjusting for age, gender, ethnicity, follow-up time, diet group, and baseline level of respective outcome trait. The associations remained similar after further controlling for concurrent weight change. In addition, we observed significant interactions between rs266717 genotype and dietary fat on changes in fasting insulin and HOMA-IR (P for interaction=0.03 for both) at 6 months with adjustment for covariates. Participants who are homozygous for T allele of rs266717 had more reductions in fasting insulin and HOMA-IR than those with other genotypes in response to the high-fat diet, but such differences were not observed in the low-fat diet group.
Conclusions: Regardless of macronutrient compositions, weight-loss diets beneficially increased circulating adiponectin, which was related to improvement of cardiometabolic profiles. Dietary fat intakes modified the effect of adiponectin variant rs266717 on improvement of insulin resistance.