Discordance between gut-derived appetite hormones and energy intake in humans

Abstract

Gut-derived hormones affect appetite and are thought to play an important role in body weight regulation. Dietary macronutrient composition can influence gut-derived appetite hormone concentrations, thereby providing theoretical basis for why some diets might facilitate weight loss better than others. We investigated postprandial gut-derived appetite hormones in 20 inpatient adults after 2 weeks of eating either a low carbohydrate (LC) or a low fat (LF) diet followed by the alternate diet in random order. A LC meal resulted in significantly greater postprandial GLP-1, GIP, and PYY but lower ghrelin compared to an isocaloric LF meal (all p≤0.02). However, differences in gut-derived appetite hormones were incommensurate with subsequent ad libitum energy intake over the rest of the day, which was 551±103 kcal (p<0.0001) greater with the LC as compared to the LF diet. The effects of gut-derived appetite hormones on ad libitum energy intake can be dominated by other diet-related factors, at least in the short-term.

Keywords: Appetite; Diet; Energy Intake; Gut Hormones; Low Carbohydrate; Low Fat; Postprandial.

Figure 1.

Postprandial responses to isocaloric low carbohydrate (LC) or low fat (LF) meals following habituation to each diet in a randomized crossover design. Mean (range) of energy in the test meals was 777 (532 to 1043) kcal. Data are mean ± SEM. n=20. p-values from paired t-test of mean postprandial plasma concentrations. (A) active glucagon-like peptide-1 (GLP-1) (B) total glucose-dependent insulinotropic polypeptide (GIP) (C) peptide YY (PYY) (D) leptin (E) total ghrelin (F) active ghrelin

Figure 2.

Total intake, and intake from lunch, dinner, and snacks throughout the day after isocaloric low carbohydrate (LC) or low fat (LF) meals following habituation to each diet in a randomized crossover design. Mean (range) of energy in the test meals was 777 (532 to 1043) kcal. Data are mean ± SEM and individual responses. n=20. p-values from paired t-test or Wilcoxon test. (A) Energy intake (EI) (kcal) (B) Mass intake (g)

Figure 3.

Comparisons between dietary macronutrient induced changes in gut hormone responses and pharmacological or bariatric surgery induced changes. (A) estimated mean active GLP-1 steady state average exposure concentrations, C_avg, achieved by low carbohydrate (LC) or low fat (LF) diet were orders of magnitude lower than the both oral and subcutaneous semaglutide using values median (90% exposure ranges) from Overgaard et al. (B) peak active GLP-1 and PYY concentrations following a LC or LF test meal were orders of magnitude lower than peak concentrations observed during a mixed-meal test following Roux-en-Y Gastric Bypass surgery (RYGB) using data from Tan et al. Data are mean ± SEM.