From the pancreas to the amygdala: new brain area critical for ingestive and motivated behavior control exerted by amylin.

iScience, Год журнала: 2025, Номер 28(3), С. 112040 - 112040

Опубликована: Фев. 17, 2025

Amylin, a pancreatic peptide, has well-established role in feeding behavior control. Amylin analogues are clinically utilized patients with diabetes and under investigation as potential anti-obesity pharmacotherapies. The neural circuits underlying actions of amylin on not well understood. While was found to bind the central amygdala (CeA) rodents primates we that all components receptors present CeA, their physiology or remains unknown. Here, investigated impact this pancreas - CeA amylin-mediated communication ingestive motivated behaviors. Activation resulted robust hypophagia, reduced food-motivated behavior, altered macronutrient preference male female rats. Clinically used analogue, pramlintide, meal size frequency by acting CeA. Disruption signaling led hyperphagia body weight gain sex divergent manner. Importantly, required for appetite suppression induced peripherally applied amylin, highlighting translational relevance brain site. Our data indicate is critical substrate signaling.

Язык: Английский

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The Chimeric Peptide (GEP44) Reduces Body Weight and Both Energy Intake and Energy Expenditure in Diet-Induced Obese Rats

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(7), С. 3032 - 3032

Опубликована: Март 26, 2025

We recently reported that a chimeric peptide (GEP44) targeting the glucagon-like peptide-1 receptor (GLP-1R) and neuropeptide Y1- Y2- receptors decreased body weight (BW), energy intake, core temperature in diet-induced obese (DIO) male female mice. In current study, we tested hypothesis strong reduction response to GEP44 is partially related stimulation of expenditure (EE). To test this, rats were maintained on high fat diet (HFD) for at least 4 months elicit DIO prior undergoing sequential 2-day vehicle period, (50 nmol/kg) minimum washout detailed measures homeostasis. reduced EE (indirect calorimetry), respiratory exchange ratio (RER), temperature, activity, BW rats. As our previous study mice, HFD-fed by 3.8 ± 0.2% 2.3 0.4%, respectively. These effects appear be mediated increased lipid oxidation reductions intake as RER cumulative The robust but not EE. paradoxical finding might secondary thermogenesis or indicate an important mechanism limit overall efficacy prevent further loss.

Язык: Английский

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MASLD: Prevalence, Mechanisms, and Sex-Based Therapies in Postmenopausal Women

Biomedicines, Год журнала: 2025, Номер 13(4), С. 855 - 855

Опубликована: Апрель 2, 2025

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic influenced by genetic, lifestyle, and environmental factors. While MASLD more prevalent in men, women are at increased risk after menopause, highlighting critical pathogenetic role of sex hormones. The complex interplay between estrogen deficiency, visceral fat accumulation, metabolic syndrome (MetS), inflammation accelerates progression, increases cardiovascular (CV) risk, triggers a cycle worsening adiposity, dysfunction, psychological problems, including eating disorders. Weight loss postmenopausal can significantly improve both outcomes, helping to prevent related conditions. This review examines prevalence MASLD, its comorbidities (type 2 diabetes T2D, CV, mental disorders), mechanisms, pharmacological treatment with GLP-1 receptor agonists (GLP1-RAs), focus on women. Given use GLP1-RAs obesity T2D patients, increase MetS this analyzes potential stable GLP-1–estrogen conjugate as therapeutic approach subgroup. By combining synergistic effects hormones, dual agonist has been shown food intake reward suppression, resulting greater weight improved insulin sensitivity, glucose, lipid metabolism. Therefore, we hypothesize that pharmacotherapy may provide targeted benefits than either hormone alone protecting liver, β-cells, overall health. As these only supported preclinical data, highlights need for future research evaluate confirm mechanisms efficacy clinical settings, particularly

Язык: Английский

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An inhibitory GLP-1 circuit in the lateral septum modulates reward processing and alcohol intake in rodents

EBioMedicine, Год журнала: 2025, Номер 115, С. 105684 - 105684

Опубликована: Апрель 17, 2025

Язык: Английский

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