We hypothesized that melatonin (Mel) supplementation may offer therapeutic benefits for obesity, particularly in women. Therefore, the study evaluated Mel's effects on white adipose tissue (WAT) in diet-induced obese female mice. Four-week-old C57BL/6 females were assigned to either a control diet (C group) or a high-fat diet (HF group) for 6 weeks (n = 20/group).
View Article and Find Full Text PDFLife Sci
January 2025
The study aimed to verify the effect of Tirzepatide (Tzp, a dual agonist GIP/GLP-1) on intestinal health and microbiota balance in an obese diabetic ovariectomized (Ovx) mice model. Female C57BL/6 mice with Ovx and diet-induced obesity with diabetes were treated with Tzp (10 nmol/kg) for four weeks. Control (C) and obese-diabetic subgroups (Od) were formed (group abbreviations: O, Ovx; T, Tzp; n = 30/group): C, CT, CO, COT, Od, OdT, OdO, OdOT.
View Article and Find Full Text PDFThe pancreas suffers from lipotoxicity, which threatens the survival of pancreatic islets. Dual peroxisome proliferator-activated receptor-alpha/gamma (PPAR-α/γ) agonism is a promising method for treating type 2 diabetes mellitus (T2DM). This study evaluated the effects of single PPAR-α and PPAR-γ or their combined activation on pancreatic islet remodelling, beta cell proliferation, identity and maintenance in an experimental obesity model.
View Article and Find Full Text PDFWe studied the effect of semaglutide (glucagon-like peptide type 1 agonist) on hypothalamic pro-inflammatory genes in diet-induced obese mice. Male C57BL/6J mice were fed a control (C) or high-fat (HF) diet for 16 weeks, then divided into six groups and maintained for an additional four-week study: C, C+semaglutide (CS), C pair-feeding (CP), HF, HF+semaglutide (HFS), and HF pair-feeding (HFP).Weight gain (WG), food efficiency (FE), and plasmatic biochemistry were determined.
View Article and Find Full Text PDFDiabetes Obes Metab
October 2024
Aim: Tirzepatide (Tzp), a novel dual agonist glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1, is approved for treating insulin resistance and obesity, and menopausal women consuming a high-calorie diet are a target to study the Tzp effect. Therefore, we aimed to allometrically scale body weight (BW) in Tzp-treated obese diabetic menopausal mice.
Materials And Methods: Three-month-old C57BL/6 female mice had bilateral ovariectomy (Ovx) or a sham procedure and for 12 weeks were fed a control diet or a high-fat and high sucrose diet (n = 120/each group [control (C), obese diabetic (Od), Ovx (O), sham (S), Tzp (T)]).
Fundam Clin Pharmacol
December 2024
Background: Monotherapy to treat obesity-associated liver insult is limited.
Objectives: In diet-induced obese mice showing metabolic dysfunction-associated steatotic liver disease (MASLD), we aimed to compare the combinations of sodium-glucose cotransporter-2 inhibitor (SGLT2i, empagliflozin, E), dipeptidyl peptidase-4 inhibitor (DPP4i, linagliptin, L), and glucagon-like peptide type 1 receptor agonist (GLP1RA, dulaglutide, D).
Methods: Male 3-month-old C57BL/6J mice were fed for 12 weeks in a control (C, n = 10) or high-fat (HF, n = 30) diet.
Nutr Res
June 2024
Metabolic dysfunction-associated steatotic liver disease (MASLD) has attracted increasing attention from the scientific community because of its severe but silent progression and the lack of specific treatment. Glucolipotoxicity triggers endoplasmic reticulum (ER) stress with decreased beta-oxidation and enhanced lipogenesis, promoting the onset of MASLD, whereas regular physical exercise can prevent MASLD by preserving ER and mitochondrial function. Thus, the hypothesis of this study was that high-intensity interval training (HIIT) could prevent the development of MASLD in high-fat (HF)-fed C57BL/6J mice by maintaining insulin sensitivity, preventing ER stress, and promoting beta-oxidation.
View Article and Find Full Text PDFThe increasing global prevalence and associated comorbidities need innovative approaches for type 2 diabetes mellitus (T2DM) prevention and treatment. Genetics contributes significantly to T2DM susceptibility, and genetic counseling is significant in detecting and informing people about the diabetic risk. T2DM is also intricately linked to overnutrition and obesity, and nutritional advising is beneficial to mitigate diabetic evolution.
View Article and Find Full Text PDFMaternal obesity might induce obesity and metabolic alterations in the progeny. The study aimed to determine the effect of supplementing obese mothers with Mel (Mel) on thermogenesis and inflammation. C57BL/6 female mice (mothers) were fed from weaning to 12 weeks control diet (C, 17% kJ as fat) or a high-fat diet (HF, 49% kJ as fat) and then matted with male mice fed the control diet.
View Article and Find Full Text PDFThe hypothalamic neuropeptides linked to appetite and satiety were investigated in obese mice treated with cotadutide (a dual receptor agonist of glucagon-like peptide 1 (GLP-1R)/Glucagon (GCGR)). Twelve-week-old male C57BL/6 mice were fed a control diet (C group, n = 20) or a high-fat diet (HF group, n = 20) for ten weeks. Each group was further divided, adding cotadutide treatment and forming groups C, CC, HF, and HFC for four additional weeks.
View Article and Find Full Text PDFScope: To analyze the effects of fexaramine (FEX), as an intestinal FXR agonist, on the modulation of the intestinal microbiota and ileum of mice fed a high-fat (HF) diet.
Methods And Results: Three-month-old C57Bl/6 male mice are divided into two groups and received a control (C, 10% of energy from lipids) or HF (50% of energy from lipids) diet for 12 weeks. They are subdivided into the C, C + FEX, HF, and HF + FEX groups.
We studied the effect of cotadutide, a dual agonist glucagon-like peptide 1 (GLP1)/Glucagon, on interscapular brown adipose tissue (iBAT) remodeling and thermogenesis of obese mice. Twelve-week-old male C57BL/6 mice were fed a control diet (C group, n = 20) or a high-fat diet (HF group, n = 20) for ten weeks. Then, animals were redivided, adding cotadutide treatment: C, CC, HF, and HFC for four additional weeks.
View Article and Find Full Text PDFObesity is related to several organs, but the liver is particularly affected. Adenosine monophosphate-activated protein kinase (AMPK) is a cellular energy sensor and regulator of liver lipid dysfunction and glucose metabolism. The mechanistic target of rapamycin (mTOR) is a protein kinase regulating cell growth, survival, metabolism, and immunity.
View Article and Find Full Text PDFJ Dev Orig Health Dis
August 2023
Melatonin supplementation to obese mothers during gestation and lactation might benefit the pancreatic islet cellular composition and beta-cell function in male offspring adulthood. C57BL/6 females (mothers) were assigned to two groups ( = 20/each) based on their consumption in control (C 17% kJ as fat) or high-fat diet (HF 49% kJ as fat). Mothers were supplemented with melatonin (Mel) (10 mg/kg daily) during gestation and lactation, or vehicle, forming the groups ( = 10/each): C, CMel, HF, and HFMel.
View Article and Find Full Text PDFObesity and type 2 diabetes mellitus (T2DM) cause morphofunctional alterations in pancreatic islet alpha and beta cells. Therefore, we hypothesize that the new GLP-1/Glucagon receptor dual agonist cotadutide may benefit islet cell arrangement and function. Twelve-week-old C57BL/6 male mice were fed a control diet (C, 10 % kJ fat) or a high-fat diet (HF, 50 % kJ fat) for ten weeks.
View Article and Find Full Text PDFAims: The extracellular matrix (ECM) is fundamental for the normal endocrine functions of pancreatic islet cells and plays key roles in the pathophysiology of type 2 diabetes. Here we investigated the turnover of islet ECM components, including islet amyloid polypeptide (IAPP), in an obese mouse model treated with semaglutide, a glucagon-like peptide type 1 receptor agonist.
Main Methods: Male one-month-old C57BL/6 mice were fed a control diet (C) or a high-fat diet (HF) for 16 weeks, then treated with semaglutide (subcutaneous 40 μg/kg every three days) for an additional four weeks (HFS).
Obesity, adipose tissue inflammation, and nonalcoholic fatty liver disease (NAFLD) are associated with insulin resistance and type 2 diabetes (T2D). Cotadutide is a dual agonist GLP-1/glucagon, currently in a preclinical study phase 2 that presents an anti-obesity effect. Diet-induced obese (DIO) C57BL/6 mice were treated for 4 weeks with cotadutide (30 nm/kg once a day at 14:00 h).
View Article and Find Full Text PDFAims: To investigate, in the liver of adult offspring, the possible effects of melatonin supplementation in the obese mother during pregnancy and lactation.
Main Methods: C57BL/6 females were fed with a control (C) or a high-fat (HF) diet and supplemented with melatonin (Mel) during the pregnancy and lactation, forming the groups: C, CMel, HF, and HFMel. After weaning until three months old, the offspring only received the C diet.
Brown adipose tissue (BAT) remains active in adults, oxidizing fatty acids or glucose and releasing energy in the form of heat. Brown adipocytes and enhanced thermogenesis are targets for treating obesity and its comorbidities. BAT shows high synthesis activity and secretes several signaling molecules.
View Article and Find Full Text PDFSemaglutide (GLP-1 agonist) was approved for treating obesity. Although the effects on weight loss and metabolism are known, the responses of adipocytes to semaglutide are yet limited. C57BL/6 male mice (n = 20/group) were fed a control diet (C) or a high-fat (HF) diet for 16 weeks and then separated into four groups (n = 10/group) for an additional four weeks: C, C diet and semaglutide, HF, and HF diet and semaglutide.
View Article and Find Full Text PDFThe study revisited the diet-induced obesity (DIO) mice and the nonalcoholic fatty liver disease (NAFLD) pathogenesis to serve as a translational model. Hepatic beta-oxidation pathways, lipogenesis, oxidative stress, hepatocyte apoptosis, and proliferation were investigated in obese mice. Three-month-old male mice were divided according to their diet for fifteen weeks, the control diet (C group, containing 10% energy from fat) and the high-fat diet (HF group, containing 50% energy from fat).
View Article and Find Full Text PDFClin Res Hepatol Gastroenterol
July 2022
Purpose: The liver regulates lipid metabolism. Decreasing mTOR (mechanistic target of rapamycin complex 1) and enhancing AMPK (AMP-activated protein kinase) help degrade hepatic diet-induced accumulated lipids. Therefore, the glucagon-like peptide type 1 receptor agonist (GLP-1) is indicated to treat obesity-related liver metabolic alterations.
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