Pancreatic islet cells disarray, apoptosis, and proliferation in obese mice. The role of Semaglutide treatment

Marinho, Thatiany de Souza; Martins, Fabiane Ferreira; Cardoso, Luiz E.M.; Águila, Márcia Barbosa; Mandarim-de-Lacerda, Carlos Alberto

doi:10.1016/j.biochi.2021.10.017

Cited by 25 publications

(14 citation statements)

References 55 publications

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“…Semaglutide leads to biochemical effects considered independent of weight loss in pair-feeding groups studied before. 12,13 Here, our DIO mice showed eWAT adipocyte hypertrophy, a proinflammatory adipokine profile, increased ER stress, and de novo lipogenesis.…”

Section: Discussionmentioning

confidence: 68%

“…18 Semaglutide (Ozempic; Novo Nordisk) was administered subcutaneously to mice at 40 µg/kg once every 3 days (corresponding to 1.2 µg per animal). 13,19 The stock semaglutide solution (1.34 mg/ml) was diluted in sterile 0.9% NaCl to 6.0 µg/ml so that an injection volume of 200 µl would contain 1.2 µg of the drug.…”

Section: Significance Statementmentioning

confidence: 99%

“…In the DIO mouse model, 11 semaglutide reduced plasma lipids, liver steatosis, inflammation, and overall glucose metabolism 12 . In addition, semaglutide favored pancreatic islet cell arrangement and enhanced beta‐cell mass in obese mice 13,14 …”

Section: Introductionmentioning

confidence: 99%

“…12 In addition, semaglutide favored pancreatic islet cell arrangement and enhanced beta-cell mass in obese mice. 13,14 Liraglutide (another GLP-1 analog) effects on mouse lipid metabolism differ from semaglutide, especially regarding plasma leptin and the magnitude of changes in other metabolic markers. 15 Altogether, the evidence indicates that the liraglutide action on adipocytes can not be directly transferred to semaglutide.…”

Section: Introductionmentioning

confidence: 99%

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Semaglutide (GLP‐1 receptor agonist) stimulates browning on subcutaneous fat adipocytes and mitigates inflammation and endoplasmic reticulum stress in visceral fat adipocytes of obese mice

Martins

Marinho

Cardoso

et al. 2022

Cell Biochemistry & Function

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Semaglutide (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. Epididymal white adipose tissue (eWAT) and subcutaneous white adipose tissue (sWAT) fat pads were studied with biochemistry, immunohistochemistry/fluorescence, stereology, and reverse transcription-quantitative polymerase chain reaction. In obese mice, semaglutide reduced the fat pad masses (eWAT, −55%; sWAT, −40%), plasmatic cytokines, and proinflammatory gene expressions: tumor necrosis factor-alpha (−60%); interleukin (IL)-6 (−55%); IL-1 beta (−40%); monocyte chemoattractant protein-1 (−90%); and leptin (−80%). Semaglutide also lessened endoplasmic reticulum (ER) stress genes of activating transcription factor-4 (−85%), CCAAT enhancer-binding protein homologous protein (−55%), and growth arrest and DNA damage-inducible gene 45 (−45%). The obese mice's adipocyte hypertrophy and macrophage infiltration were equally reduced by semaglutide. Semaglutide enhanced multiloculation and uncoupled protein 1 (UCP1) labeling in obese mice: peroxisome proliferator-activated receptor-alpha (+560%) and gamma (+150%), fibronectin type III domain-containing protein 5 (+215%), peroxisome proliferator-activated receptor-alpha coactivator (+110%), nuclear respiratory factor 1 (+260%), and mitochondrial transcription factor A (+120%). Semaglutide also increased thermogenetic gene expressions for the browning phenotype maintenance: beta-3 adrenergic receptor (+520%), PR domain containing 16 (+90%), and Ucp1 (+110%). In conclusion, semaglutide showed significant beneficial effects beyond weight loss, directly on fat pads and adipocytes

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Section: Discussionmentioning

confidence: 68%

Section: Significance Statementmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Semaglutide (GLP‐1 receptor agonist) stimulates browning on subcutaneous fat adipocytes and mitigates inflammation and endoplasmic reticulum stress in visceral fat adipocytes of obese mice

Martins

Marinho

Cardoso

et al. 2022

Cell Biochemistry & Function

Self Cite

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“…Factors such as physical activity, smoking, diet, and genetic conditions can lead to T2D development and progression. Obesity and insulin resistance can induce pancreatic islet hypertrophy and both α- and β-cell remodeling, disarray, and apoptosis, which can be ameliorated by fasting and anti-T2D treatments [ 45 , 46 ].…”

Section: Obesity Its Comorbidities and Associated Factorsmentioning

confidence: 99%

The Related Metabolic Diseases and Treatments of Obesity

2022

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Obesity is a chronic disease characterized by the abnormal or excessive accumulation of body fat, affecting more than 1 billion people worldwide. Obesity is commonly associated with other metabolic disorders, such as type 2 diabetes, non-alcoholic fatty liver disease, cardiovascular diseases, chronic kidney disease, and cancers. Factors such as a sedentary lifestyle, overnutrition, socioeconomic status, and other environmental and genetic conditions can cause obesity. Many molecules and signaling pathways are involved in the pathogenesis of obesity, such as nuclear factor (NF)-κB, Toll-like receptors (TLRs), adhesion molecules, G protein-coupled receptors (GPCRs), programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1), and sirtuin 1 (SIRT1). Commonly used strategies of obesity management and treatment include exercise and dietary change or restriction for the early stage of obesity, bariatric surgery for server obesity, and Food and Drug Administration (FDA)-approved medicines such as semaglutide and liraglutide that can be used as monotherapy or as a synergistic treatment. In addition, psychological management, especially for patients with obesity and distress, is a good option. Gut microbiota plays an important role in obesity and its comorbidities, and gut microbial reprogramming by fecal microbiota transplantation (FMT), probiotics, prebiotics, or synbiotics shows promising potential in obesity and metabolic syndrome. Many clinical trials are ongoing to evaluate the therapeutic effects of different treatments. Currently, prevention and early treatment of obesity are the best options to prevent its progression to many comorbidities.

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Semaglutide Attenuates Anxious and Depressive-Like Behaviors and Reverses the Cognitive Impairment in a Type 2 Diabetes Mellitus Mouse Model Via the Microbiota-Gut-Brain Axis

de Paiva,

da Silva,

Mendonça

et al. 2024

J Neuroimmune Pharmacol

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Newly conducted research suggests that metabolic disorders, like diabetes and obesity, play a signi cant role as risk factors for psychiatric disorders. This connection presents a potential avenue for creating novel antidepressant medications by repurposing drugs originally developed to address antidiabetic conditions. Earlier investigations have shown that GLP-1 analogs exhibit neuroprotective qualities in various models of neurological diseases, encompassing conditions such as Alzheimer's disease, Parkinson's disease, and stroke. Moreover, GLP-1 analogs have demonstrated the capability to enhance neurogenesis, a process recognized for its signi cance in memory formation and the cognitive and emotional aspects of information processing. Nonetheless, whether semaglutide holds e cacy as both an antidepressant and anxiolytic agent remains uncertain. To address this, our study focused on a mouse model of depression linked to type 2 diabetes induced by a High Fat Diet (HFD). In this model, we administered semaglutide (0.05mg/Kg intraperitoneally) on a weekly basis to evaluate its potential as a therapeutic option for depression and anxiety. Diabetic mice had higher blood glucose, lipidic pro le, and insulin resistance. Moreover, mice fed HFD showed higher serum IL-1β and LPS associated with impaired humor and cognition. The analysis of behavioral responses revealed that the administration of Semaglutide effectively mitigated depressive-and anxiety-like behaviors, concurrently demonstrating an enhancement in cognitive function. Additionally, Semaglutide treatment protected synaptic plasticity and reversed the hippocampal neuroin ammation induced by HFD fed, improving activation of the insulin pathway, demonstrating the protective effects of Semaglutide. We also found that Semaglutide treatment decreased astrogliosis and microgliosis in the dentate gyrus region of the hippocampus. In addition, Semaglutide prevented the DM2-induced impairments of POMC, and GPR43 and simultaneously increased the NeuN + and GLP-1R + neurons in the hippocampus. Our data also showed that Semaglutide increased the 5-HT and its receptor (5-HTT) and glutamatergic receptors in the hippocampus. At last, Semaglutide changed the gut microbiota pro le (increasing Bacterioidetes, Bacteroides acidifaciens, and Blautia coccoides) and decreased leaky gut, improving the gut-brain axis. Taken together, Semaglutide has the potential to act as a therapeutic tool for depression and anxiety.

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Pancreatic islet cells disarray, apoptosis, and proliferation in obese mice. The role of Semaglutide treatment

Cited by 25 publications

References 55 publications

Semaglutide (GLP‐1 receptor agonist) stimulates browning on subcutaneous fat adipocytes and mitigates inflammation and endoplasmic reticulum stress in visceral fat adipocytes of obese mice

Semaglutide (GLP‐1 receptor agonist) stimulates browning on subcutaneous fat adipocytes and mitigates inflammation and endoplasmic reticulum stress in visceral fat adipocytes of obese mice

The Related Metabolic Diseases and Treatments of Obesity

Semaglutide Attenuates Anxious and Depressive-Like Behaviors and Reverses the Cognitive Impairment in a Type 2 Diabetes Mellitus Mouse Model Via the Microbiota-Gut-Brain Axis

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