Endogenous glucagon‐like peptide (GLP)‐1 as alternative for GLP‐1 receptor agonists: Could this work and how?

Smits, Mark M.; Holst, Jens J.

doi:10.1002/dmrr.3699

Cited by 10 publications

(2 citation statements)

References 202 publications

(295 reference statements)

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“…43 Supraphysiological concentrations of GLP-1 achieved by infusion (∼25 to 30 pg·mL -1 ) suppress subjective appetite, but effects on subsequent ad libitum energy intake are modest compared with higher concentrations (∼100 to 240 kcal). 44,45 Together, infusion studies indicate a dose-response relationship between active GLP-1 and suppression of appetite, 46 and suggest that substantially greater increases in gut hormone concentrations are required to have meaningful effects on appetite and energy intake, likely greater than is achievable by diet interventions alone.…”

Section: Resultsmentioning

confidence: 99%

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

Hengist

Sciarrillo

Guo

et al. 2023

Preprint

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Gut-derived hormones affect appetite. Ghrelin increases hunger which decreases after food intake, whereas satiation and satiety are induced by peptide YY (PYY), glucagon-like peptide-1 (GLP-1), and perhaps glucose-dependent insulinotropic polypeptide (GIP) which are increased after food intake [1-3]. These gut-derived appetite hormones have been theorized to play a role in the weight-loss that results from bariatric surgery [4, 5] and agonists of GLP-1 and GIP receptors have become successful medical treatments for obesity [6-8]. Circulating concentrations of gut-derived appetite hormones can be influenced by dietary macronutrient composition [9-13], which provides a theoretical basis for why some diets may help facilitate weight loss better than others. We investigated inpatient adults in a randomized crossover study and demonstrated that, after 2 weeks of eating a low carbohydrate (LC) diet (75.8% fat, 10.0% carbohydrate), a LC meal resulted in significantly greater postprandial GLP-1, GIP, and PYY but lower ghrelin compared to an isocaloric low fat (LF) meal after 2 weeks of eating a LF diet (10.3% fat, 75.2% carbohydrate; all p<0.02). However, the observed differences in gut-derived appetite hormones were incommensurate with subsequent ad libitum energy intake across the day, which was 551±103 kcal (p<0.0001) greater following the LC diet as compared to the LF diet. These data suggest that other diet-related factors can dominate the effects of gut-derived appetite hormones on ad libitum energy intake, at least in the short-term.

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Section: Resultsmentioning

confidence: 99%

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

Hengist

Sciarrillo

Guo

et al. 2023

Preprint

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“…In addition to FXR, bile acids also work via the Takeda G protein-coupled receptor 5 (TGR5) [15,16] in mediating several metabolic effects of bile acids [17,18]. For instance, bile acid activation of TGR5 on entero-endocrine L cells has been demonstrated to control glucose metabolism via the release of glucagon-like peptide 1 (GLP-1) in these cells [19,20]. Whether disturbances in bile acid synthesis and the enterohepatic circulation of bile acids as seen in CTX affect GLP-1 release and glucose metabolism remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Characterization of Postprandial Bile Acid Profiles and Glucose Metabolism in Cerebrotendinous Xanthomatosis

Majait,

Meessen,

Vaz

et al. 2023

Nutrients

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Cerebrotendinous xanthomatosis (CTX) is a rare inherited disease characterized by sterol 27-hydroxylase (CYP27A1) deficiency and, thus, a lack of bile acid synthesis with a marked accumulation of 7α-hydroxylated bile acid precursors. In addition to their renowned lipid-emulgating role, bile acids have been shown to stimulate secretion of the glucose-lowering and satiety-promoting gut hormone glucagon-like peptide 1 (GLP-1). In this paper, we examined postprandial bile acid, glucose, insulin, GLP-1 and fibroblast growth factor 19 (FGF19) plasma profiles in patients with CTX and matched healthy controls. Seven patients and seven age, gender and body mass index matched controls were included and subjected to a 4 h mixed meal test with regular blood sampling. CTX patients withdrew from chenodeoxycholic acid (CDCA) and statin therapy three weeks prior to the test. Postprandial levels of total bile acids were significantly lower in CTX patients and consisted of residual CDCA with low amounts of ursodeoxycholic acid (UDCA). The postprandial plasma glucose peak concentration occurred later in CTX patients compared to controls, and patients’ insulin levels remained elevated for a longer time. Postprandial GLP-1 levels were slightly higher in CTX subjects whereas postprandial FGF19 levels were lower in CTX subjects. This novel characterization of CTX patients reveals very low circulating bile acid levels and FGF19 levels, aberrant postprandial glucose and insulin profiles, and elevated postprandial GLP-1 responses.

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Gut‐derived appetite hormones do not explain energy intake differences in humans following low‐carbohydrate versus low‐fat diets

Hengist,

Sciarrillo,

Guo

et al. 2024

Obesity

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ObjectiveThe objective of this study was to explore how dietary macronutrient composition influences postprandial appetite hormone responses and subsequent energy intake.MethodsA total of 20 adults (mean [SEM], age 30 [1] years, BMI 27.8 [1.3] kg/m2, n = 8 with normal weight, n = 6 with overweight, n = 6 with obesity) consumed a low‐fat (LF) diet (10% fat, 75% carbohydrate) and a low‐carbohydrate (LC) diet (10% carbohydrate, 75% fat) for 2 weeks each in an inpatient randomized crossover design. At the end of each diet, participants consumed isocaloric macronutrient‐representative breakfast test meals, and 6‐h postprandial responses were measured. Ad libitum energy intake was measured for the rest of the day.ResultsThe LC meal resulted in greater mean postprandial plasma active glucagon‐like peptide‐1 (GLP‐1; LC: 6.44 [0.78] pg/mL, LF: 2.46 [0.26] pg/mL; p < 0.0001), total glucose‐dependent insulinotropic polypeptide (GIP; LC: 578 [60] pg/mL, LF: 319 [37] pg/mL; p = 0.0004), and peptide YY (PYY; LC: 65.6 [5.6] pg/mL, LF: 50.7 [3.8] pg/mL; p = 0.02), whereas total ghrelin (LC: 184 [25] pg/mL, LF: 261 [47] pg/mL; p = 0.0009), active ghrelin (LC: 91 [9] pg/mL, LF: 232 [28] pg/mL; p < 0.0001), and leptin (LC: 26.9 [6.5] ng/mL, LF: 35.2 [7.5] ng/mL; p = 0.01) were lower compared with LF. Participants ate more during LC at lunch (244 [85] kcal; p = 0.01) and dinner (193 [86] kcal; p = 0.04), increasing total subsequent energy intake for the day compared with LF (551 [103] kcal; p < 0.0001).ConclusionsIn the short term, endogenous gut‐derived appetite hormones do not necessarily determine ad libitum energy intake.image

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Endogenous glucagon‐like peptide (GLP)‐1 as alternative for GLP‐1 receptor agonists: Could this work and how?

Cited by 10 publications

References 202 publications

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

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

Characterization of Postprandial Bile Acid Profiles and Glucose Metabolism in Cerebrotendinous Xanthomatosis

Gut‐derived appetite hormones do not explain energy intake differences in humans following low‐carbohydrate versus low‐fat diets

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