Disturbed Glucose Homeostasis Research Articles

Effects of environmentally relevant concentrations of florfenicol on the glucose metabolism system, intestinal microbiome, and liver metabolome of zebrafish

Florfenicol, a widely used veterinary antibiotic, has now been frequently detected in various water environments and human urines, with high concentrations. Accordingly, the ecological risks and health hazards of florfenicol are attracting increasing attention. In recent years, antibiotic exposure has been implicated in the disruption of animal glucose metabolism. However, the specific effects of florfenicol on the glucose metabolism system and the underlying mechanisms are largely unknown. Herein, zebrafish as an animal model were exposed to environmentally relevant concentrations of florfenicol for 28 days. Using biochemical and molecular analyses, we found that exposure to florfenicol disturbed glucose homeostasis, as evidenced by the abnormal levels of blood glucose and hepatic/muscular glycogen, and the altered expression of genes involved in glycogenolysis, gluconeogenesis, glycogenesis, and glycolysis. Considering the efficient antibacterial activity of florfenicol and the crucial role of intestinal flora in host glucose metabolism, we then analyzed changes in the gut microbiome and its key metabolite short-chain fatty acids (SCFAs). Results indicated that exposure to florfenicol caused gut microbiota dysbiosis, inhibited the production of intestinal SCFAs, and ultimately affected the downstream signaling pathways of SCFA involved in glucose metabolism. Moreover, non-targeted metabolomics revealed that arachidonic acid and linoleic acid metabolic pathways may be associated with insulin sensitivity changes in florfenicol-exposed livers. Overall, this study highlighted a crucial aspect of the environmental risks of florfenicol to both non-target organisms and humans, and presented novel insights into the mechanistic elucidation of metabolic toxicity of antibiotics.

Centella asiatica mitigates the detrimental effects of Bisphenol-A (BPA) on pancreatic islets

Bisphenol-A (BPA) is widely used in food packaging and household products, leading to daily human exposure and potential health risks including metabolic diseases like type 2 diabetes mellitus (T2DM). Understanding BPA's mechanisms and developing intervention strategies is urgent. Centella asiatica, a traditional herbal medicine containing pentacyclic triterpenoids, shows promise due to its antioxidant and anti-inflammatory properties, utilized for centuries in Ayurvedic therapy. We investigated the effect of Centella asiatica (CA) ethanol extract on BPA-induced pancreatic islet toxicity in male Swiss albino mice. BPA administration (10 and 100 μg/kg body weight, twice daily) for 21 days caused glucose homeostasis disturbances, insulin resistance, and islet dysfunction, which were partially mitigated by CA supplementation (200 and 400 mg/kg body weight). Additionally, heightened oxidative stress, elevated levels of proinflammatory cytokines, loss of mitochondrial membrane potential (MMP), abnormal cell cycle, and increased apoptosis were implicated in the detrimental impact of BPA on the endocrine pancreas which were effectively counteracted by CA supplementation. In summary, CA demonstrated a significant ability to mitigate BPA-induced apoptosis, modulate redox homeostasis, alleviate inflammation, preserve MMP, and regulate the cell cycle. As a result, CA emerged as a potent agent in neutralizing the diabetogenic effects of BPA to a considerable extent.

Protocol for a prospective multicentre cohort study to address the question whether diabetes and its management is still a risk factor in fast-track joint arthroplasty

IntroductionPerioperative glycaemic control is important. However, the complexity of guidelines for perioperative diabetes management is complicated due to different and novel antihyperglycaemic medications, limited procedure-specific data and lack of data...

Highlighting the effects of high-intensity interval training on the changes associated with hypertrophy, apoptosis, and histological proteins of the heart of old rats with type 2 diabetes

T2DM is known to cause disturbances in glucose homeostasis and negative changes in the heart muscle, while aging and diabetes are recognized risk factors for CVD. Given this, our study aims to investigate a method for controlling and managing CVDs induced by T2DM in elderly populations. To achieve this, we categorized 40 rats into 5 groups, including HAD (n = 8), HA (n = 8), AD (n = 8), AHT (n = 8), and ADT (n = 8). The exercise protocol consisted of eight weeks of HIIT (three sessions per week) performed at 90–95% of maximal speed. Following cardiac tissue extraction, we assessed the levels of IGF-1, PI3K, and AKT proteins using Western blot technique, and analyzed the histopathological variations of the heart tissue using H&E, Sudan Black, and Masson’s trichrome tissue staining. The histological findings from our study demonstrated that T2DM had a significant impact on the development of pathological hypertrophy and fibrosis in the heart tissue of elderly individuals. However, HIIT not only effectively controlled pathological hypertrophy and fibrosis, but also induced physiological hypertrophy in the AHT and ADT groups compared to the HA and AD groups. Results from Sudan Black staining indicated that there was an increase in lipid droplet accumulation in the cytoplasm of cardiomyocytes and their nuclei in the HA and AD groups, while the accumulation of lipid droplets decreased significantly in the AHT and ADT groups. In both the AHT group and the ADT group, a single HIIT session led to a reduction in collagen fiber accumulation and fibrotic frameworks. Our research also revealed that diabetes caused a significant elevation in the levels of IGF-1, PI3K, and AKT proteins, but after eight weeks of HIIT, the levels of these proteins decreased significantly in the training groups. Overall, our findings suggest that HIIT may be a suitable non-pharmacological approach for improving histological and physiological changes in elderly individuals with T2DM. However, we recommend further research to examine the impact of HIIT training on both healthy and diseased elderly populations.

Serum albumin adjusted calcium and fluoride among type 2 diabetes mellitus patients.

The regulation of glucose-dependent insulin secretion in pancreatic β-cells relies on calcium concentration, making it a calcium-dependent process. Disruptions in calcium homeostasis may contribute to insulin dysfunction and disturbances in glucose homeostasis, potentially playing a role in the development of type 2 diabetes mellitus (T2DM). In T2DM patients, there may be changes in fluoride metabolism due to impaired renal function. Measurement of serum albumin-adjusted calcium and is crucial since changes in albumin levels can impact the accurate estimation of true calcium.

WPŁYW WIRUSA SARS-CoV-2 NA HOMEOSTAZĘ GLUKOZY I CUKRZYCĘ

Due to the prevalence, the diversity of disease course, and the range of systems attacked by viral particles, COVID-19 pandemic turned out to be a challenging experience for both medical staff and patients all over the world. It is essential to remember that the infection affects health state and wellbeing of patients including their comorbidities and chronic conditions. The example of such wide-spread coexisting conditions is diabetes mellitus. In this paper, we evaluate the influence of SARS-CoV-2 infection and diabetes mellitus, especially considering the autoimmune diabetes mellitus type 1. The review describes possible pathomechanisms of glucose homeostasis disturbances in relation to the destruction of pancreas and other organs by viral particles. Moreover, the aim of the paper is to show a complex connection between therapeutic management of both COVID-19 and diabetes. We describe suggested consequences of glucocortycoids treatment and modifications in insulin therapy applied in diabetes mellitus type 1.

Aberrant glucose metabolism underlies impaired macrophage differentiation in glycogen storage disease typeIb.

Glycogen storage disease type Ib (GSD-Ib) is an autosomal recessive disorder caused by a deficiency in the glucose-6-phosphate (G6P) transporter (G6PT) that is responsible for transporting G6P into the endoplasmic reticulum. GSD-Ib is characterized by disturbances in glucose homeostasis, neutropenia, and neutrophil dysfunction. Although some studies have explored neutrophils abnormalities in GSD-Ib, investigations regarding monocytes/macrophages remain limited so far. In this study, we examined the impact of G6PT deficiency on monocyte-to-macrophage differentiation using bone marrow-derived monocytes from G6pt-/- mice as well as G6PT-deficient human THP-1 monocytes. Our findings revealed that G6PT-deficient monocytes exhibited immature differentiation into macrophages. Notably, the impaired differentiation observed in G6PT-deficient monocytes seemed to be associated with abnormal glucose metabolism, characterized by enhanced glucose consumption through glycolysis, even under quiescent conditions with oxidative phosphorylation. Furthermore, we observed a reduced secretion of inflammatory cytokines in G6PT-deficient THP-1 monocytes during the inflammatory response, despite their elevated glucose consumption. In conclusion, this study sheds light on the significance of G6PT in monocyte-to-macrophage differentiation and underscores its importance in maintaining glucose homeostasis and supporting immune response in GSD-Ib. These findings may contribute to a better understanding of the pathogenesis of GSD-Ib and potentially pave the way for the development of targeted therapeutic interventions.

Relation of Growth Differentiation Factor 15 (GDF 15) to Early Diabetic Nephropathy

Abstract Background Diabetic nephropathy (DN) is one of the leading causes of end-stage renal disease (ESRD) in developed countries and is becoming more prevalent globally due to the rise in the incidence of obesity and type 2 diabetes, DN is a progressive kidney disease caused by alterations in the glomerular capillary and tubular structure and function induced by the disturbed glucose homeostasis. Recent studies are conflicting regarding the sensitivity and the specificity of biomarkers currently used in practice for DN diagnosis (e.g., eGFR, albuminuria). Aim of the Work The aim of this work is to evaluate the relation of Growth Differentiation Factor 15 (GDF 15) to early Diabetic Nephropathy. For this purpose we study 90 adult diabetic patients classified into three groups: group (1); 35 patients with micro-albuminuria (UAE 30–299 mg/24 h), group (2); 35 patients with macro-albuminuria (UAE ≥ 300 mg/24 h), and group (3); 20 patients with norm-albuminuria (UAE <30 mg/24 h). It was found that there is no statistically significant difference between age and sex in the three studied groups, so patients in this study are matched in age and sex. Patients and Methods This cross-sectional comparative study involved 90 adult diabetic patients were selected from the patients attending the outpatient clinic of the Nephrology Department in Hurghada General Hospital. The study was performed at the period from January 2018 to January 2019. Results As regard the type of diabetes in our study there was statistically insignificant difference between microalbuminuric and macroalbuminuric groups in this study as regard type 1 and type 2 diabetes. Our data revealed that there is a statistically insignificant difference between the three studied groups as regard duration of diabetes, The study also showed that there was statistically insignificant difference between the two studied groups (1 & 2) as regard hypertension, while they were statistically significant compared to controls, This study showed that GDF-15 was markedly elevated in group 1 & 2 compared to control. There was statistically very highly significant difference between the two studied groups (1 & 2) and control group (3), while there is a statistically significant difference between group 1 and group 2. Conclusion In conclusion, the GDF-15 levels at the time of diagnosis have a significant negative correlation with the initial renal function and a significant positive correlation with a higher risk of disease progression in DN. Our result suggested that high GDF-15 reflects early renal injury and a mild degree of proteinuria in DN. GDF-15 is independent prediction to proteinuria level.

Quantifying postprandial glucose responses using a hybrid modeling approach: Combining mechanistic and data-driven models in The Maastricht Study.

Computational models of human glucose homeostasis can provide insight into the physiological processes underlying the observed inter-individual variability in glucose regulation. Modelling approaches ranging from "bottom-up" mechanistic models to "top-down" data-driven techniques have been applied to untangle the complex interactions underlying progressive disturbances in glucose homeostasis. While both approaches offer distinct benefits, a combined approach taking the best of both worlds has yet to be explored. Here, we propose a sequential combination of a mechanistic and a data-driven modeling approach to quantify individuals' glucose and insulin responses to an oral glucose tolerance test, using cross sectional data from 2968 individuals from a large observational prospective population-based cohort, the Maastricht Study. The best predictive performance, measured by R2 and mean squared error of prediction, was achieved with personalized mechanistic models alone. The addition of a data-driven model did not improve predictive performance. The personalized mechanistic models consistently outperformed the data-driven and the combined model approaches, demonstrating the strength and suitability of bottom-up mechanistic models in describing the dynamic glucose and insulin response to oral glucose tolerance tests.

Comparison and effect of plain and calcium fortified yogurt on glycemic responses, anthropometrics and metabolic biomarkers

Metabolic syndromes including obesity and diabetes are the most common health issues due to insulin resistance, disturbance in glucose homeostasis, lack of exercise, and improper diet. The current study was planned to evaluate the potential effects of regular diet with fortified yogurt on blood glycemia and anthropometric responses. Plain yogurt was procured from the local market, and then it was fortified with calcium. Furthermore, the subsequent effect of fortified yogurt on blood glucose, insulin, and anthropometric measurements was assessed at different time intervals. A total of 40 healthy females and males aged about 20 years with a normal BMI range (20–24.9 kg/m2) were recruited within the Government College University Faisalabad. Participants filled out the habits Performa, stress factors questionnaire, and activity questionnaire. Blood glucose (BG) and visual analogous scale (VAS) performs were also taken in the fasting stage and then assigned treatment was given. After 15, 30, 45, 60, 90, and 120 min intervals VAS and BG estimation was carried out. The results shows that fortified yogurt contained a higher amount of calcium. Likewise, a similar trend was observed for the desire to eat, a feeling of fullness, palatability, physical comfort, and overall acceptability. The results obtained from various analyses were statistically evaluated.

A holistic view of muscle metabolic reprogramming through personalized metabolic modeling in newly diagnosed diabetic patients.

Type 2 diabetes mellitus (T2DM) is a challenging and progressive metabolic disease caused by insulin resistance. Skeletal muscle is the major insulin-sensitive tissue that plays a pivotal role in blood sugar homeostasis. Dysfunction of muscle metabolism is implicated in the disturbance of glucose homeostasis, the development of insulin resistance, and T2DM. Understanding metabolism reprogramming in newly diagnosed patients provides opportunities for early diagnosis and treatment of T2DM as a challenging disease to manage. Here, we applied a system biology approach to investigate metabolic dysregulations associated with the early stage of T2DM. We first reconstructed a human muscle-specific metabolic model. The model was applied for personalized metabolic modeling and analyses in newly diagnosed patients. We found that several pathways and metabolites, mainly implicating in amino acids and lipids metabolisms, were dysregulated. Our results indicated the significance of perturbation of pathways implicated in building membrane and extracellular matrix (ECM). Dysfunctional metabolism in these pathways possibly interrupts the signaling process and develops insulin resistance. We also applied a machine learning method to predict potential metabolite markers of insulin resistance in skeletal muscle. 13 exchange metabolites were predicted as the potential markers. The efficiency of these markers in discriminating insulin-resistant muscle was successfully validated.

The antidiabetic effect of superparamagnetic iron oxidenanoparticles highlights the role of WNT/AMPK/mTOR/FOXO1/mitochondrialDNA in muscle and kidney.

Aim: To explore the antidiabetic effect of superparamagnetic iron oxide nanoparticles (SPIONs)-PEG-550 and its related metabolic pathways in muscles and kidney. Materials & methods: Diabetes was induced in 5-day neonatal rats; after confirming diabetes, treatment with SPIONs-PEG-550 started at different doses for 4weeks. Routine analysis of glucose, insulin, adipocytokines, urea and creatinine was performed. The expression of several genes involved in metabolic pathways and the corresponding protein levels were examined. Results & conclusion: SPIONs-PEG-550 normalized the disturbed glucose homeostasis, reversed insulin resistance, adjusted the serum level of adipocytokines, andimproved several disturbed downstream effectors of the insulin signaling and WNT pathway in both tissues. Histological examination of the muscle and pancreas has shown almost normal functional characteristics without remarkable adverse effects on the kidney.

SXRF for Studying the Distribution of Trace Metals in the Pancreas and Liver.

Transition metals such as iron, copper and zinc are required for the normal functioning of biological tissues, whereas others, such as cadmium, are potentially highly toxic. Any disturbances in homeostasis caused by lack of micronutrients in the diet, pollution or genetic heredity result in malfunction and/or diseases. Here, we used synchrotron X-ray fluorescence, SXRF, microscopy and mice with altered functions of major antioxidant enzymes to show that SXRF may become a powerful tool to study biologically relevant metal balance in the pancreas and liver of mice models with disturbed glucose homeostasis.

Exposure to per- and polyfluoroalkyl substances in early pregnancy, risk of gestational diabetes mellitus, potential pathways, and influencing factors in pregnant women: A nested case-control study

Although previous studies have reported an association between maternal serum perfluoroalkyl substance (PFAS) exposure and gestational diabetes mellitus (GDM) risk, results have been inconsistent. Few studies have focused on the combined effects of emerging and legacy PFASs on glucose homeostasis while humans are always exposed to multiple PFASs simultaneously. Moreover, the potential pathways by which PFAS exposure induces GDM are unclear. A total of 295 GDM cases and 295 controls were enrolled from a prospective cohort of 2700 pregnant women in Shanghai, China. In total, 16 PFASs were determined in maternal spot serum samples in early pregnancy. We used conditional logistic regression, multiple linear regression, and Bayesian kernel machine regression (BKMR) to examine individual and joint effects of PFAS exposure on GDM risk and oral glucose tolerance test outcomes. The mediating effects of maternal serum biochemical parameters, including thyroid and liver function were further assessed. Maternal perfluorooctanoic acid (PFOA) exposure was associated with an increased risk of GDM (odds ratio (OR) = 1.68; 95% confidence interval (95% CI): 1.10, 2.57), consistent with higher concentrations in GDM cases than controls. Based on mediation analysis, an increase in the free triiodothyronine to free thyroxine ratio partially explained the effect of this association. For continuous glycemic outcomes, positive associations were observed between several PFASs and 1-h and 2-h glucose levels. In BKMR, PFAS mixture exposure showed a positive trend with GDM incidence, although the CIs were wide. These associations were more pronounced among women with normal pre-pregnancy body mass index (BMI). Mixed PFAS congeners may affect glucose homeostasis by increasing 1-h glucose levels, with perfluorononanoic acid found to be a main contributor. Exposure to PFASs was associated with increased risk of GDM and disturbance in glucose homeostasis, especially in normal weight women. The PFAS-associated disruption of maternal thyroid function may alter glucose homeostasis.

The Official Journal of ATTD Advanced Technologies & Treatments for Diabetes Conference 22‐25 February 2023 I Berlin & Online

The Official Journal of ATTD Advanced Technologies & Treatments for Diabetes Conference 22‐25 February 2023 I Berlin & Online

P27Kip1 Deficiency Impairs Brown Adipose Tissue Function Favouring Fat Accumulation in Mice.

The aim of this work was to investigate the effect of the whole-body deletion of p27 on the activity of brown adipose tissue and the susceptibility to develop obesity and glucose homeostasis disturbances in mice, especially when subjected to a high fat diet. p27 knockout (p27-/-) and wild type (WT) mice were fed a normal chow diet or a high fat diet (HFD) for 10-weeks. Body weight and composition were assessed. Insulin and glucose tolerance tests and indirect calorimetry assays were performed. Histological analysis of interscapular BAT (iBAT) was carried out, and expression of key genes/proteins involved in BAT function were characterized by qPCR and Western blot. iBAT activity was estimated by 18F-fluorodeoxyglucose (18FDG) uptake with microPET. p27-/- mice were more prone to develop obesity and insulin resistance, exhibiting increased size of all fat depots. p27-/- mice displayed a higher respiratory exchange ratio. iBAT presented larger adipocytes in p27-/- HFD mice, accompanied by downregulation of both Glut1 and uncoupling protein 1 (UCP1) in parallel with defective insulin signalling. Moreover, p27-/- HFD mice exhibited impaired response to cold exposure, characterized by a reduced iBAT 18FDG uptake and difficulty to maintain body temperature when exposed to cold compared to WT HFD mice, suggesting reduced thermogenic capacity. These data suggest that p27 could play a role in BAT activation and in the susceptibility to develop obesity and insulin resistance.

Capsaicin ameliorates diet-induced disturbances of glucose homeostasis and gut microbiota in mice associated with the circadian clock.

Glucose metabolism disorder triggered by a high-energy diet is associated with circadian disruption in the brain, peripheral tissues and gut microbiota. The present study aims to investigate the regulating effects of capsaicin (CAP) on the diet-induced disturbances of glucose homeostasis and gut microbiota in respect of circadian rhythm-related mechanisms. Our results indicated that CAP significantly ameliorated glucose metabolism disorder in mice induced by a high-fat and high-fructose diet (HFFD). The rhythmic expressions of circadian clock genes (Bmal1, Clock, and others) and glucose metabolism-related genes (Pgc-1α, Glut2, G6pc, and Pepck) in the liver disrupted by an abnormal diet were also recovered by CAP. Microbial studies using 16S rDNA sequencing revealed that CAP modulated the structure and composition of gut microbiota and improved the circadian oscillations of Firmicutes and Bacteroidetes at the phylum level and Allobaculum, Bacteroides, Bifidobacterium, and Alistipes at the genus level. Correlation analysis indicated that a close correlation existed between intestinal microbiota, hepatic circadian gene expressions and the level of glucose metabolism-related factors, indicating that CAP could alleviate HFFD-induced disturbances of glucose metabolism and gut microbiota associated with circadian clock related mechanisms.

The glucocorticoid dexamethasone inhibits HIF-1α stabilization and metabolic reprogramming in lipopolysaccharide-stimulated primary macrophages.

Synthetic glucocorticoids are used to treat many chronic and acute inflammatory conditions. Frequent adverse effects of prolonged exposure to glucocorticoids include disturbances of glucose homeostasis caused by changes in glucose traffic and metabolism in muscle, liver, and adipose tissues. Macrophages are important targets for the anti-inflammatory actions of glucocorticoids. These cells rely on aerobic glycolysis to support various pro-inflammatory and antimicrobial functions. Employing a potent pro-inflammatory stimulus in two commonly used model systems (mouse bone marrow-derived and human monocyte-derived macrophages), we showed that the synthetic glucocorticoid dexamethasone inhibited lipopolysaccharide-mediated activation of the hypoxia-inducible transcription factor HIF-1α, a critical driver of glycolysis. In both cell types, dexamethasone-mediated inhibition of HIF-1α reduced the expression of the glucose transporter GLUT1, which imports glucose to fuel aerobic glycolysis. Aside from this conserved response, other metabolic effects of lipopolysaccharide and dexamethasone differed between human and mouse macrophages. These findings suggest that glucocorticoids exert anti-inflammatory effects by impairing HIF-1α-dependent glucose uptake in activated macrophages. Furthermore, harmful and beneficial (anti-inflammatory) effects of glucocorticoids may have a shared mechanistic basis, depending on the alteration of glucose utilization.

Phenolic fraction concentrates supplementation ameliorates learning and memory impairments in chronically stressed streptozotocin-diabetic rats by reducing brain tumor necrosis factor-α

Introduction: The present work aims to assess if insulin combined with phenolic fraction concentrates (PFCs) prevents diabetes-related cognitive impairments by controlling neuroinflammation in streptozotocin-induced diabetic rats exposed to chronic mild stress (CMS). Methods: Directly after confirming the hyperglycemia, diabetic animals were treated with insulin combined with PFC and were exposed to 2 stressors/day for 12 weeks. Then, four cognitive tests were carried out to assess learning and memory performances. Finally, the rats were anesthetized, blood samples were collected for corticosterone and Tumor necrosis factor alpha (TNF-α) analysis, and the brain regions viz. striatum, hippocampus, and prefrontal-cortex of each hemisphere were dissected out for TNF-α analysis. Results: Both diabetes and stress could induce learning and memory impairments, which were more prominent in stressed diabetic animals, and significantly reversed by insulin treatment supplemented with PFC compared to the insulin monotherapy. Moreover, diabetic rats exposed to CMS displayed disturbances in glucose homeostasis as well as corticosterone secretion. These dysfunctions were linked to the significant increase of TNF-α in the blood as well as in the prefrontal cortex, hippocampus, and striatum. Insulin significantly ameliorated this inflammatory abnormality, while the supplemented treatment showed a significant effect, by stabilizing TNF-α to its normal levels in the hippocampus and in the blood when compared to insulin monotherapy. Conclusion: Insulin supplemented with PFC has a favorable effect over insulin alone on inflammatory aberrations linked with type 1 diabetes and stress in animals, confirming the preference of the combined treatment over insulin for the management of cognitive impairment in stressed diabetic subjects.

Irisin improves adiposity and exercise tolerance in a rat model of postmenopausal obesity through enhancing adipo-myocyte thermogenesis

The prevalence of obesity and its associated metabolic disorders, along with their healthcare costs, is rising exponentially. Irisin, an adipomyokine, may serve as a critical cross-organ messenger, linking skeletal muscle with adipose tissue and the liver to integrate the energy homeostasis under diet-induced obesity. We aimed to explore the putative role of irisin in the protection against obesity in a postmenopausal rat model by modulating energy expenditure (EE). Bilateral ovariectomy (OVX) was performed. After 3 weeks of recovery, the OVX rats were classified according to their dietary protocol into rats maintained on normal diets (ND) (OVX) or high-fat diet (HFD) groups. The HFD-fed animals were equally divided into OVX/HFD, or irisin-treated OVX/HFD groups. Sham rats, maintained on ND, were selected as the control group. We evaluated anthropometric, EE, and molecular biomarkers of browning and thermogenesis in inguinal white adipose tissue and skeletal muscle, and the activity of the proteins related to mitochondrial long chain fatty acid transport, oxidation, and glycolysis. HFD of OVX further deteriorated the disturbed glucose homeostasis, lipid profile, and the reduced irisin, thermogenic parameters in adipose tissue and skeletal muscle, and EE. Irisin treatment improved the lipid profile and insulin resistance. That was associated with reduced hepatic gluconeogenic enzyme activities and restored hepatic glycogen content. Irisin reduced ectopic lipid infiltration. Irisin augmented EE by activating non-shivering thermogenesis in muscle and adipose tissues and decreasing metabolic efficiency. Our experimental evidence suggests irisin’s use as a potential thermogenic agent, therapeutically targeting obesity in postmenopausal patients.Graphical abstractIrisin modulates the non-shivering thermogenesis in skeletal muscle and adipose tissue in postmenopausal model