Increased Body Weight and Fat Mass After Subchronic GIP Receptor Antagonist, but Not GLP-2 Receptor Antagonist, Administration in Rats

Baldassano, Sara; Gasbjerg, Lærke S.; Kizilkaya, Hüsün Sheyma; Rosenkilde, Mette M.; Holst, Jens J.; Hartmann, Bolette

doi:10.3389/fendo.2019.00492

Cited by 26 publications

(21 citation statements)

References 83 publications

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“…The presence of GIP receptor has been demonstrated in the adipose tissue, while GLP-1 receptor does not appear to be relevant [ 50 ]. Several studies have shown that GIP plays a role in the metabolism of adipose tissue by increasing the entry of FFA into adipocytes with a consequent reduction in their plasma levels ( Figure 2 ).…”

Section: Role Of Gpcrs In the Metabolism Of Peripheral Tissuesmentioning

confidence: 99%

Atypical Antipsychotics and Metabolic Syndrome: From Molecular Mechanisms to Clinical Differences

et al. 2021

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Atypical antipsychotics (AAPs) are commonly prescribed medications to treat schizophrenia, bipolar disorders and other psychotic disorders. However, they might cause metabolic syndrome (MetS) in terms of weight gain, dyslipidemia, type 2 diabetes (T2D), and high blood pressure, which are responsible for reduced life expectancy and poor adherence. Importantly, there is clear evidence that early metabolic disturbances can precede weight gain, even if the latter still remains the hallmark of AAPs use. In fact, AAPs interfere profoundly with glucose and lipid homeostasis acting mostly on hypothalamus, liver, pancreatic β-cells, adipose tissue, and skeletal muscle. Their actions on hypothalamic centers via dopamine, serotonin, acetylcholine, and histamine receptors affect neuropeptides and 5′AMP-activated protein kinase (AMPK) activity, thus producing a supraphysiological sympathetic outflow augmenting levels of glucagon and hepatic glucose production. In addition, altered insulin secretion, dyslipidemia, fat deposition in the liver and adipose tissues, and insulin resistance become aggravating factors for MetS. In clinical practice, among AAPs, olanzapine and clozapine are associated with the highest risk of MetS, whereas quetiapine, risperidone, asenapine and amisulpride cause moderate alterations. The new AAPs such as ziprasidone, lurasidone and the partial agonist aripiprazole seem more tolerable on the metabolic profile. However, these aspects must be considered together with the differences among AAPs in terms of their efficacy, where clozapine still remains the most effective. Intriguingly, there seems to be a correlation between AAP’s higher clinical efficacy and increase risk of metabolic alterations. Finally, a multidisciplinary approach combining psychoeducation and therapeutic drug monitoring (TDM) is proposed as a first-line strategy to avoid the MetS. In addition, pharmacological treatments are discussed as well.

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Section: Role Of Gpcrs In the Metabolism Of Peripheral Tissuesmentioning

confidence: 99%

Atypical Antipsychotics and Metabolic Syndrome: From Molecular Mechanisms to Clinical Differences

et al. 2021

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“…Human cross-linked C-terminal telopeptides of type I collagen (ß-CTX) were measured by an enzyme-linked immunosorbent assay (Catalog Number: EH3989, Fine-Biotech), as previously reported [ 46 ]. Assay values were corrected for urinary dilution by urinary creatinine concentration.…”

Section: Methodsmentioning

confidence: 99%

Analysis of Body Perception, Preworkout Meal Habits and Bone Resorption in Child Gymnasts

Amato

Proia

Caldara

et al. 2021

IJERPH

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The beneficial effects of physical activity on body image perception and bone are debated among artistic gymnasts. Gymnasts seem to be at greater risk of developing body dissatisfaction, eating disorders and osteoporosis due to inadequate nutrition and attention to the appearance of the body. The objective of this work was to investigate the association between the artistic gymnast and a more favorable body image compared to their sedentary peers and if a preworkout high-carbohydrate meal (HCM; 300 kcal, 88% carbohydrates, 9% protein, 3% fat) or high-protein meal (HPM; 300 kcal, 55% carbohydrates, 31% protein, 13% fat) is able to attenuate bone resorption in young rhythmic gymnasts. Twenty-eight preadolescent female gymnasts were examined. Self-esteem tests were used to analyze body image perception. Preworkout eating habits were examined by short food frequency questions (FFQ) validated for children. The biomarker of the bone resorption C-terminal telopeptide region of collagen type 1 (CTX) was measured in the urine (fasting, postmeal and postworkout). Gymnasts reported higher satisfaction with their body appearance compared to sedentary peers. Of the gymnasts, 30% did not have a preworkout meal regularly, and the timing of the consumption was variable. Bone resorption was decreased by the HCM, consumed 90 min before the training, with respect to the HPM. The study suggests that playing artistic gymnastics is associated with a positive body self-perception in a child. The variability in preworkout meal frequency and timing need attention to prevent inadequate eating habits in light of the ability of the HCM to reduce acute bone resorption.

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“…It is important to note that the effect of GIP(3–30) to fully block GIPR activity in a physiologically relevant system is incomplete [ 31 ], and this peptide is not comparable in potency or reliability to the well-characterized GLP-1R antagonist exendin (9–39) [ 16 ]. In rats, administration of GIP(3–30) for 3 weeks did not alter body weight or food intake [ 71 ], although the short duration of the study and the delivery of a rapidly cleared peptide complicates the interpretation of these results. However, a different acylated peptide antagonist of the GIPR with a longer half-life that provides chronic antagonism failed to lower body weight over a 10-day period [ 72 ].…”

Section: Gipr Loss Of Functionmentioning

confidence: 99%

Targeting the GIPR for obesity: To agonize or antagonize? Potential mechanisms

Campbell

2021

Molecular Metabolism

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Background Glucose-dependent insulinotropic peptide (GIP) is one of two incretin hormones that communicate nutrient intake with systemic metabolism. Although GIP was the first incretin hormone to be discovered, the understanding of GIP's biology was quickly outpaced by research focusing on the other incretin hormone, glucagon-like peptide 1 (GLP-1). Early work on GIP produced the theory that GIP is obesogenic, limiting interest in developing GIPR agonists to treat type 2 diabetes. A resurgence of GIP research has occurred in the last five years, reinvigorating interest in this peptide. Two independent approaches have emerged for treating obesity, one promoting GIPR agonism and the other antagonism. In this report, evidence supporting both cases is discussed and hypotheses are presented to reconcile this apparent paradox. Scope of the review This review presents evidence to support targeting GIPR to reduce obesity. Most of the focus is on the effect of singly targeting the GIPR using both a gain- and loss-of-function approach, with additional sections that discuss co-targeting of the GIPR and GLP-1R. Major conclusions There is substantial evidence to support that GIPR agonism and antagonism can positively impact body weight. The long-standing theory that GIP drives weight gain is exclusively derived from loss-of-function studies, with no evidence to support that GIPR agonisms increases adiposity or body weight. There is insufficient evidence to reconcile the paradoxical observations that both GIPR agonism and antagonism can reduce body weight; however, two independent hypotheses centered on GIPR antagonism are presented based on new data in an effort to address this question. The first discusses the compensatory relationship between incretin receptors and how antagonism of the GIPR may enhance GLP-1R activity. The second discusses how chronic GIPR agonism may produce desensitization and ultimately loss of GIPR activity that mimics antagonism. Overall, it is clear that a deeper understanding of GIP biology is required to understand how modulating this system impacts metabolic homeostasis.

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Increased Body Weight and Fat Mass After Subchronic GIP Receptor Antagonist, but Not GLP-2 Receptor Antagonist, Administration in Rats

Cited by 26 publications

References 83 publications

Atypical Antipsychotics and Metabolic Syndrome: From Molecular Mechanisms to Clinical Differences

Atypical Antipsychotics and Metabolic Syndrome: From Molecular Mechanisms to Clinical Differences

Analysis of Body Perception, Preworkout Meal Habits and Bone Resorption in Child Gymnasts

Targeting the GIPR for obesity: To agonize or antagonize? Potential mechanisms

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