Hepatic, adipocyte, enteric and pancreatic hormones: response to dietary macronutrient composition and relationship with metabolism

Background: We sought to characterize the effects of dietary macronutrient composition on various hormones implicated in the regulation of insulin sensitivity (IS) and energy expenditure (EE). Methods: Following 10-15% weight loss, 21 overweight subjects consumed 3 weight-loss maintenance diets [low fat (LF), low glycemic index (LGI) and very low carbohydrate (VLC)] in random order, each for 4 weeks. At baseline and at the end of each treatment period, fasting samples for fibroblast growth factor (FGF)-21, heme-oxygenase-1 (HO-1), chemerin, irisin, secreted frizzle-related protein (SFRP-4), total bile acids, ghrelin, gastrin inhibitory peptide (GIP), peptide-Y, and amylin; hepatic and peripheral IS; and EE were obtained. Analyses were controlled for age, gender, baseline body mass index, and diet sequence. Results: FGF-21 decreased (P < 0.0001), with differential effect by macronutrient composition (mean change from baseline +/- SEM: LF-49.4 +/- 16.6, LGI-58.6 +/- 16.3, VLC-76.7 +/- 18.2 pg/mL, P = 0.0002). Change in FGF-21 was inversely associated with change in hepatic IS [Beta =-0.565 units/log(ng/mL), P = 0.02], but not with peripheral IS or EE. Heme-oxygenase-1 (HO-1) increased (P = 0.003), without differential effect by macronutrient composition (LF 0.40 +/- 0.26, LGI 0.98 +/- 0.63, VLC 0.49 +/- 0.29 ng/mL, P = 0.07). Ghrelin increased (P = 0.0003), while chemerin decreased (P = 0.001) without macronutrient effect. Total bile acid, irisin, SFRP-4, GIP, peptide-Y and amylin levels did not change. Conclusions: FGF-21 levels decreased with dietary intervention in proportion to carbohydrate content, and correlated with hepatic insulin sensitivity, suggesting a pattern of improving FGF-21 resistance. HO-1 increased in response to dietary intervention, a tendency to greater increase in response to the LGI diet. Dietary intervention affected ghrelin and chemerin, independent of macronutrient composition. These findings may elucidate relationships between dietary composition, insulin sensitivity and metabolism.