Body Insulin Resistance Research Articles

Efecto de semaglutida sobre los biomarcadores de la enfermedad del hígado graso en pacientes con diabetes y obesidad

AimThis work aims to assess the effect of weekly subcutaneous semaglutide on biomarkers of metabolic-associated fatty liver disease (MAFLD), namely the hepatic steatosis index (HSI) and the fibrosis-4 (FIB-4) index, at 24weeks in outpatients attended to in internal medicine departments. MethodsThis study analyzed patients in an ongoing, multicenter, prospective, pre-post, uncontrolled cohort registry that enrolls unique, consecutive patients with type2 diabetes treated with weekly subcutaneous semaglutide. Steatosis/fibrosis were determined by HSI (<30 ruled out, >36 steatosis) and FIB-4 (<1.3 ruled out, >2.67 fibrosis), respectively. ResultsThe sample included 213 patients (46.9% women) with a median age of 64 (±19) years. The median baseline body mass index and weight were 36.1 (±8.4) kg/m2 and 98 (±26.9) kg, respectively. A total of 99.9% had HSI values indicating steatosis, with a mean HSI of 47.9 (±8.2). Additionally, 10.8% had fibrosis (FIB-4 >2.67) and 42.72% had values in intermediate ranges (FIB-4 1.3-2.67). At 24weeks, there was a significant reduction in HSI (−2.36 (95%CI: 1.83-2.9), p<0.00001) and FIB-4 (−0.075 (95%CI: 0.015-0.14), p<0.016), mainly related to declines in body weight, triglyceride levels, insulin resistance (estimated by the triglyceride-glucose index), and liver enzymes. ConclusionThese results show that weekly subcutaneous semaglutide had a beneficial effect on liver steatosis that went beyond glucose control. Its effects were mainly related to weight loss, a decline in biomarkers, and improvements in insulin sensitivity. For many patients, early detection is essential for improving MAFLD outcomes and may allow for selecting the most efficient treatment options.

A review analysis of exercise training regimes among females with polycystic ovary syndrome

Objective: The current systematic review was planned to provide quality assessment of different exercise regimes and their outcomes on the symptoms of polycystic ovary syndrome, and to see if one exercise regime was better than the rest. Methods: Search was conducted on PubMed and Google Scholar databases for studies published between 2001 and 2021 whose full text was available. The search yielded 28 studies that were reviewed. Results: The current evidence suggests that exercise regimes, such as high-intensity interval training, progressive resistance training, aerobic exercises, and yoga may improve polycystic ovary syndrome conditions. This is accomplished through treating associated risk factors, like body morphology, insulin resistance, hyperandrogenism, lipid profile, reproductive hormones, menstrual cycle, and quality of life. Conclusion: Exercise regimes improves several symptoms of polycystic ovary syndrome. However, selecting a specific exercise regime over others as the standardised treatment protocol remained inconclusive. Key Words: Polycystic ovarian syndrome, Exercises, High-intensity interval training, Aerobic exercises.

MSR1 is not required for obesity-associated inflammation and insulin resistance in mice

Obesity induces a chronic inflammatory state associated with changes in adipose tissue macrophages (ATMs). Macrophage scavenger receptor 1 (MSR1) has been implicated in the regulation of adipose tissue inflammation and diabetes pathogenesis; however, reports have been mixed on the contribution of MSR1 in obesity and glucose intolerance. We observed increased MSR1 expression in VAT of obese diabetic individuals compared to non-diabetic and single nuclear RNA sequencing identified macrophage-specific expression of MSR1 in human adipose tissue. We examined male Msr1−/− (Msr1KO) and WT controls and observed protection from obesity and AT inflammation in non-littermate Msr1KO mice. We then evaluated obese littermate Msr1+/− (Msr1HET) and Msr1KO mice. Both Msr1KO mice and Msr1HET mice became obese and insulin resistant when compared to their normal chow diet counterparts, but there was no Msr1-dependent difference in body weight, glucose metabolism, or insulin resistance. Flow cytometry revealed no significant differences between genotypes in ATM subtypes or proliferation in male and female mice. We observed increased frequency of proliferating ATMs in obese female compared to male mice. Overall, we conclude that while MSR1 is a biomarker of diabetes status in human adipose tissue, in mice Msr1 is not required for obesity-associated insulin resistance or ATM accumulation.

Liraglutide on type 2 diabetes mellitus with nonalcoholic fatty liver disease: A systematic review and meta-analysis of 16 RCTs.

Nonalcoholic fatty liver disease (NAFLD) is a common comorbidity of type 2 diabetes mellitus (T2DM). Our aim is to investigate the effects of liraglutide on T2DM with NAFLD. Relevant articles published from the earliest publication to March 2022 were selected from several databases. The Cochrane Collaboration's RevMan software was used for the analysis. Sixteen studies are selected for this meta-analysis, which includes totally 634 patients in the treatment group and 630 patients in the control group. As a result, 14 studies show that fasting plasma glucose levels of the experimental group are lower than that of the control group; 15 studies show that glycosylated hemoglobin A1c levels of the experimental group are lower than that of the control group; 13 studies show that triglyceride levels of the experimental group are lower than that of the control group; twelve studies show that total cholesterol levels of the experimental group are lower than that of the control group; 10 studies show that alanine aminotransferase levels of the experimental group is lower than that of the control group; 10 studies show that no significant difference in changes in aspartate transaminase between 2 groups; 13 studies show that low density lipoprotein cholesterol levels of the experimental group is lower than that of the control group; 9 studies show that no significant difference in changes in high density lipoprotein cholesterol between 2 groups; 7 studies mentioned adverse effects and the difference is significant. Liraglutide is potentially curative for T2DM with NAFLD.

Body adiposity markers and insulin resistance in patients with type 1 diabetes.

Body composition changes are associated with adverse effects such as increased insulin resistance (IR) in individuals with diabetes mellitus. This study aims to evaluate the association between different body adiposity markers and IR in adults with type 1 diabetes (T1D). The cross-sectional study included outpatient adults with T1D from a university public hospital in southern Brazil. The body adiposity markers studied were waist circumference (WC), waist-height ratio (WHtR), body mass index (BMI), conicity index (CI), lipid accumulation product (LAP) and body adiposity index (BAI). IR was calculated using an Estimated Glucose Disposal Rate (EGDR) equation (analyzed in tertiles), considering an inverse relation between EGDR and IR. Poisson regression models were used to estimate the odds ratio (OR) and 95% CIs of association of adiposity markers with IR. A total of 128 patients were enrolled (51% women), with a median EGDR of 7.2 (4.4-8.7) mg.kg-1.min-1. EGDR was negatively correlated with WC (r = -0.36, p < 0.01), WHtR (r = -0.39, p < 0.01), CI (r = -0.44, p < 0.01), LAP (r = -0.41, p < 0.01) and BMI (r = -0.24, p < 0.01). After regression analyses, WC (OR = 2.07; CIs: 1.12-3.337; p = 0.003), WHtR (OR = 2.77; CIs: 1.59-4.79; p < 0.001), CI (OR = 2.59; CIs: 1.43-4.66; p = 0.002), LAP (OR = 2.27; CIs: 1.25-4.11; p = 0.007) and BMI (OR = 1.78; CIs: 1.09-2.91; p = 0.019) remained associated with IR. The authors suggest using the studied adiposity markers as a routine since they were shown to be suitable parameters in association with IR.

Unraveling the Potential Role of Tecomella undulata in Experimental NASH.

The pathophysiology of nonalcoholic steatohepatitis (NASH) is complex, owing to its diverse pathological drivers and, until recently, there were no approved drugs for this disease. Tecomella is a popular herbal medicine used to treat hepatosplenomegaly, hepatitis, and obesity. However, the potential role of Tecomella undulata in NASH has not yet been scientifically investigated. The administration of Tecomella undulata via oral gavage lowered body weight, insulin resistance, alanine transaminase (ALT), aspartate transaminase (AST), triglycerides, and total cholesterol in western diet sugar water (WDSW) fed mice but had no effect on chow diet normal water (CDNW) fed mice. Tecomella undulata improved steatosis, lobular inflammation, and hepatocyte ballooning and resolved NASH in WDSW mice. Furthermore, Tecomella undulata also alleviated the WDSW-induced Endoplasmic Reticulum stress and oxidative stress, enhanced antioxidant status, and thus reduced inflammation in the treated mice. Of note, these effects were comparable to saroglitazar, the approved drug used to treat human NASH and the positive control used in the study. Thus, our findings indicate the potential of Tecomella undulata to ameliorate WDSW-induced steatohepatitis, and these preclinical data provide a strong rationale for assessing Tecomella undulata for the treatment of NASH.

Chronic physiologic hyperglycemia impairs insulin-mediated suppression of plasma glucagon concentration in healthy humans

Background and aimsHyperglucagonemia is a characteristic feature of type 2 diabetes mellitus (T2DM). We examined the effect of chronic (48–72 h) physiologic increase (+50 mg/dl) in plasma glucose concentration on suppression of plasma glucagon concentration by insulin and by hyperglycemia in normal glucose tolerance (NGT) individuals. Materials and methodsStudy One: 16 NGT subjects received OGTT and 3-step hyperinsulinemic (10, 20, 40 mU/m2·min) euglycemic clamp before and after 48 hour glucose infusion to increase plasma glucose by ~50 mg/dl. Study Two: 20 NGT subjects received OGTT and 2-step hyperglycemic (+125 and + 300 mg/dl) clamp before and after 72 hour glucose infusion. Plasma insulin, C-peptide and glucagon concentrations were measured during OGTT, euglycemic hyperinsulinemic and hyperglycemic clamps. Ratio of plasma glucagon/insulin was used as an index of insulin-mediated suppression of glucagon secretion. ResultsDuring all 3 insulin clamp steps (Study 1), plasma glucagon concentration was increased compared to baseline study, and plasma glucagon/insulin ratio was significantly reduced by 24 % (p < 0.05). The rate of insulin-stimulated glucose disposal was inversely correlated with plasma glucagon/insulin ratio (r = −0.44, p < 0.05) and with glucagon AUC (r = −0.48, p < 0.05). During the 2-step hyperglycemic clamp (Study 2) plasma glucagon was similar before and after 72 h of glucose infusion; however, glucagon/insulin ratio was significantly reduced (p < 0.05). Incremental area under plasma insulin curve during the first (r = −0.74, p < 0.001) and second (r = −0.85, p < 0.001) hyperglycemic clamp steps was strongly and inversely correlated with plasma glucagon/insulin ratio. ConclusionSustained (48–72 h) physiologic hyperglycemia (+50 mg/dl) caused whole body insulin resistance and impaired insulin-mediated suppression of glucagon secretion, suggesting a role for glucotoxicity in development of hyperglucagonemia in T2DM.

The Relationship between Bone Mineral Densitometry and Visceral Adiposity Index in Postmenopausal Women.

It was aimed to compare visceral adiposity index (VAI) levels in patients with normal bone mineral density (BMD), osteopenia, and osteoporosis. One hundred twenty postmenopausal women (40 with normal BMD, 40 with osteopenia, and 40 with osteoporosis) between the ages of 50 to 70 years were included in the study. For females, the VAI was calculated using the formula (waist circumference [WC]/[36.58 + (1.89 x body mass index (BMI))]) x (1.52/High-density lipoprotein [HDL]-cholesterol [mmol/L]) x (triglyceride [TG]/0.81 [mmol/L]). The time of menopause from the beginning was similar in all groups. Waist circumference was found to be higher in those with normal BMD than in the osteopenic and osteoporotic groups (p = 0.018 and p < 0.001, respectively), and it was also higher in the osteopenic group than in the osteoporotic group (p = 0.003). Height and body weight, BMI, blood pressure, insulin, glucose, HDL-cholesterol, and homeostasis model assessment-insulin resistance (HOMA-IR) levels were similar in all groups. Triglyceride levels were found to be higher in the normal BMD group, compared with the osteoporotic group (p = 0.005). The level of VAI was detected as higher in those with normal BMD, compared with the women with osteoporosis (p = 0.002). Additionally, the correlation analysis showed a positive correlation between dual-energy X-ray absorptiometry (DXA) spine T-scores, WC, VAI, and a negative correlation between DXA spine T-scores and age. In our study, we found higher VAI levels in those with normal BMD, compared with women with osteoporosis. We consider that further studies with a larger sample size will be beneficial in elucidating the entity.

The Neuronal and Non-Neuronal Pathways of Sodium-Glucose Cotransporter-2 Inhibitor on Body Weight-Loss and Insulin Resistance.

With the emergence of sodium-glucose cotransporter 2 inhibitors (SGLT2i), the treatment of type 2 diabetes mellitus (T2DM) has achieved a new milestone, of which the insulin-independent mechanism could produce weight loss, improve insulin resistance (IR) and exert other protective effects. Besides the well-acknowledged biochemical processes, the dysregulated balance between sympathetic and parasympathetic activity may play a significant role in IR and obesity. Weight loss caused by SGLT-2i could be achieved via activating the liver-brain-adipose neural axis in adipocytes. We previously demonstrated that SGLT-2 are widely expressed in central nervous system (CNS) tissues, and SGLT-2i could inhibit central areas associated with autonomic control through unidentified pathways, indicating that the role of the central sympathetic inhibition of SGLT-2i on blood pressure and weight loss. However, the exact pathway of SGLT2i related to these effects and to what extent it depends on the neural system are not fully understood. The evidence of how SGLT-2i interacts with the nervous system is worth exploring. Therefore, in this review, we will illustrate the potential neurological processes by which SGLT2i improves IR in skeletal muscle, liver, adipose tissue, and other insulin-target organs via the CNS and sympathetic nervous system/parasympathetic nervous system (SNS/PNS).

An Original Asteraceae Based Infused Drink Prevents Metabolic Syndrome in Fructose-Rat Model.

Metabolic syndrome (METS) is a complex disorder that predisposes an affected person to an increased risk of diabetes and cardiovascular disease. Bitter Asteraceae plants contain several compounds active against METS that can be used as an alternative preventive therapy. Our previous work showed that a natural chicory extract (NCRAE) containing chicoric acid (CRA) and chlorogenic acid (CGA) in a molar ratio of 70/30 exhibited an antioxidant, insulin sensitization and anti-hyperglycemic effect. The present study was designed to evaluate the preventive effects of an NCRAE-like extract against METS in a complementary natural pharmacotherapeutic approach. An original Asteraceae infused drink containing the NCRAE CRA/CGA molecular ratio equivalent was prepared from dandelion (Taraxacum officinale L.) and burdock (Arctium lappa L.). The anti-METS effect of this drink was evaluated on the fructose-rat model for 8 weeks. Body weight, blood biochemistry, hepatic glucose-6-phosphatase, arterial blood pressure glucose and insulin tolerance were evaluated after 8 weeks. Our results show that daily oral intake of the Asteraceae infused drink led to a reduction of body weight gain, hyperglycemia, hypertriglyceridemia, insulin resistance and hypertension. Moreover, rat-by-rat analysis of the insulinemia measures revealed two types of responders. One sub-group of subjects demonstrated normal insulinemia and the other subgroup demonstrated hyperinsulinemia. This hyperinsulinemia, associated with the inhibition of the glucose-6-phosphatase activity in the liver tissue, may suggest an insulin release caused by CGA. The present study suggests that this original infusion of dandelion leaves and burdock roots may be used as an adjuvant therapy to prevent metabolic syndrome.

The Effect of Early Time-Restricted Eating vs Later Time-Restricted Eating on Weight Loss and Metabolic Health.

It remains controversial whether the choice of the daily eating window early or later in time-restricted eating (TRE) intervention (early or later TRE) has different effects on weight loss and metabolic health. A network meta-analysis was performed to evaluate the efficacy between early and later TRE in adults with obesity or overweight. We searched PubMed, Embase, Web of Science, and Cochrane Library for randomized controlled trials (RCTs) published until October 16, 2022. We conducted a network meta-analysis to evaluate the efficacy of early and later TRE on body weight and metabolic parameters, including glycemic metabolism, blood pressure, and lipid profiles. Twelve RCTs with 730 obese or overweight adults were included in this meta-analysis. Early TRE and later TRE both elicited moderate reductions in body weight and insulin resistance (IR) (homeostasis model assessment of IR) when compared to non-TRE. Interestingly, early TRE showed more effectiveness than later TRE in improving IR (early vs later TRE: -0.44; 95% CI, -0.86 to -0.02; P < .05), whereas no statistically significant difference was detected in weight loss (early vs later TRE: -0.31 kg; 95% CI, -1.15 to 0.53 kg; P >.05). In addition, early TRE rather than later TRE showed significant benefits in glycemic metabolism and blood pressure when compared to non-TRE. No significant differences between early and later TRE were observed for fasting blood glucose, blood pressure, and lipid profiles. This meta-analysis suggests that people may choose early TRE for more effective weight management and metabolic benefits. Nevertheless, further large-scale RCTs are warranted to verify our findings.

Effects of neutral polysaccharide from Platycodon grandiflorum on high-fat diet-induced obesity via the regulation of gut microbiota and metabolites.

The obesity epidemic has become a global problem with far-reaching health and economic impact. Despite the numerous therapeutic efficacies of Platycodon grandiflorum, its role in modulating obesity-related metabolic disorders has not been clarified. In this study, a purified neutral polysaccharide, PGNP, was obtained from Platycodon grandiflorum. Based on methylation and NMR analyses, PGNP was found to be composed of 2,1-β-D-Fruf residues ending with a (1→2)-bonded α-D-Glcp. The protective effects of PGNP on high-fat HFD-induced obesity were assessed. According to our results, PGNP effectively alleviated the signs of metabolic syndrome, as demonstrated by reductions in body weight, hepatic steatosis, lipid profile, inflammatory response, and insulin resistance in obese mice. Under PGNP treatment, intestinal histomorphology and the tight junction protein, ZO-1, were well maintained. To elucidate the underlying mechanism, 16S rRNA gene sequencing and LC-MS were employed to assess the positive influence of PGNP on the gut microbiota and metabolites. PGNP effectively increased species diversity of gut microbiota and reversed the HFD-induced imbalance in the gut microbiota by decreasing the Firmicutes to Bacteroidetes ratio. The abundance of Bacteroides and Blautia were increased after PGNP treatment, while the relative abundance of Rikenella, Helicobacter were reduced. Furthermore, PGNP notably influenced the levels of microbial metabolites, including the increased levels of cholic and gamma-linolenic acid. Overall, PGNP might be a potential supplement for the regulation of gut microbiota and metabolites, further affecting obesity.

Metabolic and Molecular Response to High-Fat Diet Differs between Rats with Constitutionally High and Low Serotonin Tone.

Maintaining energy balance is a complex physiological function whose dysregulation can lead to obesity and associated metabolic disorders. The bioamine serotonin (5HT) is an important regulator of energy homeostasis, with its central and peripheral pools influencing energy status in opposing ways. Using sublines of rats with constitutionally increased (high-5HT) or decreased (low-5HT) whole-body 5HT tone, we have previously shown that under standard diet constitutionally higher 5HT activity is associated with increased body weight, adiposity, and impaired glucose homeostasis. Here, we investigated the response of 5HT sublines to an obesogenic diet. Consistent with previous findings, high-5HT animals fed a standard diet had poorer metabolic health. However, in response to a high-fat diet, only low-5HT animals increased body weight and insulin resistance. They also showed more pronounced changes in blood metabolic parameters and the expression of various metabolic genes in hypothalamus and adipose tissue. On the other hand, high-5HT animals appeared to be protected from major metabolic disturbances of the obesogenic diet. The results suggest that constitutionally low 5HT activity is associated with higher susceptibility to harmful effects of a high-energy diet. High-5HT subline, which developed less adverse metabolic outcomes on hypercaloric diets, may prove useful in understanding metabolically healthy obesity in humans.

4-Methylumbelliferone Targets Revealed by Public Data Analysis and Liver Transcriptome Sequencing.

4-methylumbelliferone (4MU) is a well-known hyaluronic acid synthesis inhibitor and an approved drug for the treatment of cholestasis. In animal models, 4MU decreases inflammation, reduces fibrosis, and lowers body weight, serum cholesterol, and insulin resistance. It also inhibits tumor progression and metastasis. The broad spectrum of effects suggests multiple and yet unknown targets of 4MU. Aiming at 4MU target deconvolution, we have analyzed publicly available data bases, including: 1. Small molecule library Bio Assay screening (PubChemBioAssay); 2. GO pathway databases screening; 3. Protein Atlas Database. We also performed comparative liver transcriptome analysis of mice on normal diet and mice fed with 4MU for two weeks. Potential targets of 4MU public data base analysis fall into two big groups, enzymes and transcription factors (TFs), including 13 members of the nuclear receptor superfamily regulating lipid and carbohydrate metabolism. Transcriptome analysis revealed changes in the expression of genes involved in bile acid metabolism, gluconeogenesis, and immune response. It was found that 4MU feeding decreased the accumulation of the glycogen granules in the liver. Thus, 4MU has multiple targets and can regulate cell metabolism by modulating signaling via nuclear receptors.

Environmental endocrine disruptor Bisphenol A induces metabolic derailment and obesity via upregulating IL-17A in adipocytes

BackgroundBisphenol A (BPA), a ubiquitous environmental endocrine disruptor, has been extensively demonstrated to be associated with metabolic disorders, including obesity and type 2 diabetes mellitus. However, the underlying mechanism underpinning the environmental etiology of chronic metabolic disorders has not been sufficiently elucidated. ObjectivesThis study is designed to explore the toxicological pathogenesis of chronic inflammation in BPA exposure during obesity. MethodsWe investigated the role of IL-17A in the association of BPA exposure and obesity from human cross-sectional study to animal models, including genetically modified IL-17A-/- mice. ResultsHere, our work started from case-control observation that BPA exposure was significantly associated with risk of obesity (odds ratio = 4.72, 95%CI: 3.18 – 11.18, P < 0.01), metabolic disorder and levels of interleukin-17A (IL-17A) in human adipose (estimated changes β = 0.46, 95%CI: 0.15 – 1.01, P < 0.01) with bariatric surgery. Animal model fed with high-fat diet (HFD) confirmed that BPA exposure aggravated body weight gain and insulin resistance, concurrent with much heightened inflammatory responses in the adipose tissue including increase in IL-17A and macrophage polarization towards M1 stage. Genetically modified IL-17A ablated mice (IL-17A-/-) showed reversed adipose tissue inflammation response, improved macrophage polarization homeostasis, along with insulin sensitivity in both HFD group alone or much more significantly the HFD + BPA group. Moreover, mediation analysis in human epidemiological investigation demonstrated that plasma IL-17A attributed up to 30.01% mediating role in the associations between BPA exposure and obesity risk. DiscussionThis research paradigm from human to animal provides strong evidence for the elucidation of IL-17A moderating inflammation and insulin resistance in obesity. Such findings reiterate the obesogenic role of environmental endocrine disruptor BPA in metabolic disorders and unveils the potential toxicological mechanisms underpinning such effect.

Relationship between body composition, insulin resistance, and hormonal profiles in women with polycystic ovary syndrome.

To investigate how body fat influences glucose metabolism and hormone profiles in women with polycystic ovary syndrome (PCOS), compared to women without PCOS. We conducted a cross-sectional study of 166 women with PCOS and 139 age-matched control women at Peking University Third Hospital (Beijing, China) from March 2016 to December 2021. All participants underwent bioimpedance rate assessment of clinical, anthropometric, hormonal, and metabolic features. In particular, body composition parameters were assessed, based on the methods used in a previous study. Homeostasis model assessment-insulin resistance (HOMA-IR) and other indices calculated from fasting glucose and insulin were used to measure insulin resistance. The hormonal profiles [follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrogen (E2), prolactin (PRL), total testosterone (T), and androstenedione (A2)] were assessed by using biochemical methods. Two subgroup analyses were conducted according to waist-to-hip ratio (WHR; < 0.85, non-central obesity and ≥ 0.85, central obesity) and body fat percentage (BFP; < 35% for lean and ≥35% for obesity). The indices above were analyzed using a two-sided t-test or Wilcoxon rank sum test. Linear regression was used to investigate the effects of body composition on metabolism and sex hormones in the PCOS and control groups. Compared to women without PCOS, women with PCOS and central obesity (P=0.021), PCOS and noncentral obesity (P<0.001), PCOS and high BFP (P<0.001), and PCOS and low BFP (P<0.001) had more severe glucose metabolism evaluated with HOMA-IR. Women with PCOS experienced greater insulin sensitivity impairment than did the normal population for every equal increase in BFP. LH, LH/FSH, total testosterone, and androstenedione were significantly higher in patients with PCOS than in healthy controls, regardless of WHR and BFP stratification. However, negative correlations existed between body fat indices (i.e., BFP and body mass index) and hormone indices (i.e., LH and androstenedione) in the PCOS group, but were absent in the control group. Obese and non-obese women with PCOS have more severe insulin resistance and sex-hormone disorders than women without PCOS. The effect of body fat on sex-hormone disorders is only exist in women with PCOS. These findings suggested that PCOS clinical guidelines should be more specific to body fat. https://clinicaltrials.gov/, Registration No. NCT04264832.

Therapeutic Effect of Tinospora cordifolia (Willd) Extracts on Letrozole-Induced Polycystic Ovarian Syndrome and its Complications in Murine Model.

Tinosopora cordifolia (Willd) (TC) is commonly used in Ayurvedic medicine since long time for number of ailments and its preparations are also considered by food safety and standards authority of India as nutritional supplement. However the scientific evidence on its possible safety and efficacy in polycystic ovarian syndrome and associated complications was not studied in detail. The purpose of this investigation is to examine whether or not TC can have therapeutic effects on letrozole induced PCOS and related complications such as body weight, dyslipidaemia, glucose tolerance, hormonal regulation, insulin resistance and sensitivity, severity of PCOS and histopathological changes in ovary using mice animal model. Present study is a preclinical study involving laboratory animals. After verifying the absence of PCOS, the animals began receiving Letrozole, which lasted for 21 days. Fasting blood glucose (FBG), the oral glucose tolerance test (OGTT), triglycerides, cholesterol, and weight were recorded. The levels of hormones like oestrogen, progesterone, insulin, testosterone, luteinising hormone (LH) and follicle stimulating hormone (FSH), histopathology was carried out. The Institutional Animal Ethics Committee at DITU gave its clearance to the animal experimentation on July 10, 2021 (DITU/IAEC/21-22/07-06). The majority of cornified epithelial cells were seen in groups treated with TC extract during the estrous phase of the cycle. Mice exposed to TC retained normal body weight. FBG, 1- and 2-hour OGTT, triglyceride and cholesterol levels were all significantly improved by extracts. Estradiol, progesterone, testosterone, insulin, LH and FSH concentration were all corrected in TC-treated animals. The HOMA-IR, HOMA-Beta and QUICKI values were also corrected with TC extracts. The morphological and microscopic features of the ovary were also greatly enhanced. Based on these findings, we conclude that treating PCOS mice with TC extracts significantly ameliorates the disease and severity down to nil-to-moderate levels by reducing hyperinsulinemia, hyperandrogenism, dyslipidaemia, enhancing insulin sensitivity, correcting oestrogen, progesterone, LH and FSH levels via enhanced ovarian function. Further molecular and cellular level of study is recommended for further elaboration of mechanism of action. • Tinospora cordifolia satva, oil and hydroalcoholic extract were studied in letrozole-induced PCOS in mice model• Anti PCOS efficacy of 3 preparations studied with respect to their mechanism of action in detail• For the first time proposing method of calculating severity of PCOS in animal model• Tinospora cordifolia oil preparation completely reversed PCOS effect of letrozole and made them normal• Histopathological and morphological studies support the biochemical claims.

5-Heptadecylresorcinol alleviated high-fat diet induced obesity and insulin resistance by activating brown adipose tissue.

The whitening and loss of brown adipose tissue (BAT) during obesity and aging are associated with a higher risk of metabolic syndrome and chronic diseases. 5-Heptadecylresorcinol (AR-C17), the specific biomarker of whole-grain wheat and rye intake, has been proved to have notable health promoting effects, whereas whether AR-C17 could modulate BAT function and the potential mechanism of action remains unclear. In this study, we found that AR-C17 could significantly inhibit body weight gain and insulin resistance in high-fat diet (HFD) induced obese mice. Moreover, AR-C17 treatment improved whole body energy metabolism and alleviated the whitening and loss of BAT compared with the HFD group. RNA sequencing and western-blot analysis indicated that expression of genes and proteins related to BAT energy metabolism was upregulated by AR-C17 administration, including AMPK, UCP-1, ACSL1, CPT1A, and SIRT3. These results suggested that brown adipose tissue might be the target of AR-C17 to prevent obesity and its associated insulin resistance.

Gender features of metabolic syndrome components in young age

The article analyzes the clinical and laboratory features of young men and women with abdominal obesity and metabolic syndrome. The study was carried out on 173 patients of both sexes aged 18-45 years. The patients were divided into 3 groups: group 1 – isolated abdominal obesity (AO); group 2 – combination of abdominal obesity with 1 of the metabolic syndrome components (AO+1); group 3 – metabolic syndrome (MetS). It was found that in young men, the values of carbohydrate (glucose, insulin) and lipid metabolism (HDL cholesterol, LDL cholesterol, triglycerides), insulin resistance indices (HOMA-IR, TyG) in the AO and AO+1 groups were homogeneous. However, the ratio of TG/HDL in the AO+1 group exceeded the value of the AO group. Women in the AO+1 group showed changes relative to the group of women with isolated AO that are hyperglycemia, increased LDL cholesterol, insulin resistance (increased TG/HDL) and dysfunction of visceral adipose tissue (increased VAI). Young men with MetS are characterized by excess body weight, hyperglycemia, dyslipidemia (increased LDL cholesterol and triglycerides), insulin resistance (as measured by TyG and TG/HDL), and dysfunction of visceral adipose tissue. The gender feature of women is the development of MetS on the background of obesity, dysfunction of visceral adipose tissue and insulin resistance in combination with deeper changes in lipid metabolism (increased LDL cholesterol and triglycerides, as well as a decrease in HDL cholesterol).

High-Intensity Interval Training Versus Moderate-Intensity Continuous Training for Improving Physical Health in Elderly Women.

In elderly women, a lack of regular physical exercise may result in faster decreases in general health and functional performance. Although high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) have been effectively applied in young and clinical groups, there is no evidence to support their use in elderly women to achieve health benefits. Thus, the major goal of this study was to investigate how HIIT affected health-related outcomes in elderly women. Twenty-four inactive elderly women agreed to participate in the 16-week HIIT and MICT intervention. Body composition, insulin resistance, blood lipids, functional capacity, cardiorespiratory fitness, and quality of life were all measured before and after the intervention. The number of differences between groups was determined using Cohen's effect sizes, and the pre-post intra-group changes were compared using paired t-tests. Using 2 × 2 ANOVA, the time × group interaction effects between HIIT and MICT were evaluated. Body fat percentage, sagittal abdominal diameter, waist circumference, and hip circumference all were improved significantly in the 2 groups. HIIT substantially improved fasting plasma glucose and cardiorespiratory fitness as compared to the MICT. HIIT improved the lipid profile and functional ability more significantly compared to the MICT group. These findings show that HIIT is a useful exercise for improving elderly women's physical health.