Abstract
BackgroundWe sought to characterize the effects of dietary macronutrient composition on various hormones implicated in the regulation of insulin sensitivity (IS) and energy expenditure (EE).MethodsFollowing 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.ResultsFGF-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.ConclusionsFGF-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.Trial registrationNCT00315354.
Highlights
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)
Fibroblast growth factor (FGF)-21 levels are elevated in humans with obesity and type 2 diabetes mellitus [7], in association with markers of metabolic syndrome, which suggests a pattern of FGF-21 resistance [8] that may comprise a fourth component of the obesity-related resistance triad of insulin, leptin and sympathetic tone
While the exact mechanism by which FGF-21 responds to nutrient intake is unclear, FGF-21 is stimulated by free fatty acid (FFA) [33], insulin [33] and ketones [34], and is necessary for changes in lipid and glucose metabolism induced by very low carbohydrate diets [35]
Summary
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). Previous data suggest that dietary composition modulates weight-loss induced changes in energy expenditure, insulin sensitivity and satiety. Administration of FGF-21 to humans modestly decreases body weight [5], and in animal models improves insulin sensitivity, energy expenditure and hepatic steatosis [6], with maximal effect at low doses. FGF-21 levels are elevated in humans with obesity and type 2 diabetes mellitus [7], in association with markers of metabolic syndrome, which suggests a pattern of FGF-21 resistance [8] that may comprise a fourth component of the obesity-related resistance triad of insulin, leptin and sympathetic tone. FGF21 levels decrease with bariatric surgery [9], the effect of diet induced weight loss has not been wellcharacterized
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