Gut Peptide Agonism in the Treatment of Obesity and Diabetes

Grandl, Gerald; Novikoff, Aaron; DiMarchi, Richard D.; Tschöp, Matthias H.; Müller, Timo

doi:10.1002/cphy.c180044

Cited by 6 publications

(4 citation statements)

References 379 publications

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“…In the past few years, much effort has been put into developing combinatorial approaches that target food intake and energy expenditure pathways (including those directed toward insulin sensitivity), which have shown very promising results ( 196 , 197 ). Some of these approaches combine gut peptide agonism to treat obesity and its associated disorders and have been demonstrated to be effective at reducing weight, improving glucose homeostasis, and ameliorating the content of fatty acids in the liver of diet-induced obese mice ( 198 , 199 , 200 ). Some of the gut peptide-based multi-agonists initially investigated in preclinical models of obesity are currently under phase I or II clinical trials (see review ( 196 )), which will likely produce the main next-generation pharmacological agents to be used.…”

Section: Discussionmentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: The gut–brain axis: regulating energy balance independent of food intake

Nogueiras

2021

European Journal of Endocrinology

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Obesity is a global pandemic with a large health and economic burden worldwide. Body weight is regulated by the ability of the central nervous system, and specially the hypothalamus, to orchestrate the function of peripheral organs that play a key role in metabolism. Gut hormones play a fundamental role in the regulation of energy balance, as they modulate not only feeding behavior but also energy expenditure and nutrient partitioning. This review examines the recent discoveries about hormones produced in the stomach and gut, which have been reported to regulate food intake and energy expenditure in preclinical models. Some of these hormones act on the hypothalamus to modulate thermogenesis and adiposity in a food intake–independent fashion. Finally, I discuss the association in humans of these gut hormones to eating, energy expenditure, and weight loss after bariatric surgery.

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Section: Discussionmentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: The gut–brain axis: regulating energy balance independent of food intake

Nogueiras

2021

European Journal of Endocrinology

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“…The insulinotropic and anorexigenic actions of GLP-1 make it an appealing candidate for the treatment of obesity. 3 However, the mechanism by which GLP-1 improves obesity remains unclear. Some reports suggest that this mechanism may be associated with the regulation of adipokine synthesis within adipose tissue.…”

Section: Impact Statementmentioning

confidence: 99%

“…The insulinotropic and anorexigenic actions of GLP-1 make it an appealing candidate for the treatment of obesity. 3…”

Section: Introductionmentioning

confidence: 99%

Progress in the contrary effects of glucagon-like peptide-1 and chemerin on obesity development

Zhang,

Ye,

Wang

2023

Exp Biol Med (Maywood)

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Glucagon-like peptide-1 (GLP-1), secreted by intestinal L-cells, plays a pivotal role in the modulation of β-cell insulin secretion in a glucose-dependent manner, concurrently promoting β-cell survival and β-cell mass. Notably, GLP-1 has emerged as an effective second-line treatment for type 2 diabetes mellitus, gaining further prominence for its pronounced impact on body weight reduction, positioning it as a potent antiobesity agent. However, the mechanism by which GLP-1 improves obesity remains unclear. Some reports suggest that this mechanism may be associated with the regulation of adipokine synthesis within adipose tissue. Chemerin, a multifunctional adipokine and chemokine, has been identified as a pivotal player in adipocyte differentiation and the propagation of systemic inflammation, a hallmark of obesity. This review provides a comprehensive overview of the mechanisms by which GLP-1 and chemerin play crucial roles in obesity and obesity-related diseases. It discusses well-established aspects, such as their effects on food intake and glycolipid metabolism, as well as recent insights, including their influence on macrophage polarization and adipose tissue thermogenesis. GLP-1 has been shown to increase the population of anti-inflammatory M2 macrophages, promote brown adipose tissue thermogenesis, and induce the browning of white adipose tissue. In contrast, chemerin exhibits opposite effects in these processes. In addition, recent research findings have demonstrated the promising potential of GLP-1-based therapies in directly or indirectly regulating chemerin expression. In an intriguing reciprocal relationship, chemerin has also been newly identified as a negative regulator of GLP-1 in vivo. This review delineates the intricate interplay between GLP-1 and chemerin, unraveling their mutual inhibitory interactions. To the best of our knowledge, no previous reviews have focused on this specific topic, making this review particularly valuable in expanding our understanding of the endocrine mechanisms of obesity and providing potential strategies for the treatment of obesity and related diseases.

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“…Unfortunately, only limited data exist on the physiological distribution of GIH concentrations and on intra-individual variations of GIH levels in healthy non-obese individuals. So far, GIH levels were mainly measured in association with bariatric surgery [10][11][12][13][14][15], obesity [16], and T2D [17][18][19], either in a longitudinal design or one day after medication or supraphysiological GIH injections [17,18,[20][21][22]. Most studies that examined healthy nonobese individuals had small sample sizes, and participants were often tested only once after ingestion or infusion of nutrients, GIHs, or their antagonists [23][24][25].…”

Section: Introductionmentioning

confidence: 99%

Gastrointestinal Hormones in Healthy Adults: Reliability of Repeated Assessments and Interrelations with Eating Habits and Physical Activity

et al. 2021

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Background: Gastrointestinal hormones (GIHs) are crucial for the regulation of a variety of physiological functions and have been linked to hunger, satiety, and appetite control. Thus, they might constitute meaningful biomarkers in longitudinal and interventional studies on eating behavior and body weight control. However, little is known about the physiological levels of GIHs, their intra-individual stability over time, and their interaction with other metabolic and lifestyle-related parameters. Therefore, the aim of this pilot study is to investigate the intra-individual stability of GIHs in normal-weight adults over time. Methods: Plasma concentrations of ghrelin, leptin, GLP-1 (glucagon-like-peptide), and PP (pancreatic polypeptide) were assessed by enzyme-linked immunosorbent assay (ELISA) in 17 normal-weight, healthy adults in a longitudinal design at baseline and at follow-up six months later. The reliability of the measurements was estimated using intra-class correlation (ICC). In a second step, we considered the stability of GIH levels after controlling for changes in blood glucose and hemoglobin A1 (HbA1c) as well as self-reported physical activity and dietary habits. Results: We found excellent reliability for ghrelin, good reliability for GLP1 and PP, and moderate reliability for leptin. After considering glucose, HbA1c, physical activity, and dietary habits as co-variates, the reliability of ghrelin, GLP1, and PP did not change significantly; the reliability of leptin changed to poor reliability. Conclusions: The GIHs ghrelin, GLP1, and PP demonstrated good to excellent test–retest reliability in healthy individuals, a finding that was not modified after adjusting for glucose control, physical activity, or dietary habits. Leptin showed only moderate to poor reliability, which might be linked to weight fluctuations, albeit small, between baseline and follow-up assessment in our study sample. Together, these findings support that ghrelin, GLP1, and PP might be further examined as biomarkers in studies on weight control, with GLP1 and PP serving as anorexic markers and ghrelin as an orexigenic marker. Additional reliability studies in obese individuals are necessary to verify or refute our findings for this cohort.

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Gut Peptide Agonism in the Treatment of Obesity and Diabetes

Cited by 6 publications

References 379 publications

MECHANISMS IN ENDOCRINOLOGY: The gut–brain axis: regulating energy balance independent of food intake

MECHANISMS IN ENDOCRINOLOGY: The gut–brain axis: regulating energy balance independent of food intake

Progress in the contrary effects of glucagon-like peptide-1 and chemerin on obesity development

Gastrointestinal Hormones in Healthy Adults: Reliability of Repeated Assessments and Interrelations with Eating Habits and Physical Activity

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