The Effects of Exercise Interventions on Ectopic and Subcutaneous Fat in Patients with Type 2 Diabetes Mellitus: A Systematic Review, Meta-Analysis, and Meta-Regression.

Background/Objectives: The aim of the present study was to determine the effects of exercise training on ectopic and subcutaneous fat in patients with type 2 diabetes mellitus (T2DM). Methods: Web of Science, PubMed, and Scopus were searched for original articles published through November 2023 that included exercise versus control interventions on body mass (BM), liver fat percentage, visceral fat area (VFA), subcutaneous fat area (SFA), and intramuscular fat volume or mass (IMF) in patients with T2DM. Weighted mean differences (WMDs) for liver fat and BM, standardized mean differences (SMDs) for VFA, SFA, and IMF, and 95% confidence intervals (95% CIs) were determined using random-effects models. Results: Thirty-six studies comprising 2110 patients with T2DM were included in the present meta-analysis. Exercise training effectively reduced BM [WMD = -2.502 kg, p = 0.001], liver fat% [WMD = -1.559%, p = 0.030], VFA [SMD = -0.510, p = 0.001], and SFA [SMD = -0.413, p = 0.001] in comparison to the control. The IMF [SMD = 0.222, p = 0.118] remained unchanged compared to the controls. Subgroup analyses showed that the type of exercise, duration, and body mass index (BMI) of participants were sources of heterogeneity. Conclusions: The current meta-analysis provides strong evidence that exercise training, particularly aerobic and combined (aerobic and resistance) exercise programs, is effective for reducing BM, VFA, and SFA in patients with T2DM. However, aerobic exercise was more effective for reducing liver fat than combined exercise. The beneficial effects of exercise on VFA and SFA reduction, but not liver fat, are associated with weight loss. These findings highlight the importance of including consistent exercise as a key management component for T2DM and associated ectopic fat deposition, with potential long-term benefits for metabolic health.

The effects of probiotic supplementation and exercise training on liver enzymes and cardiometabolic markers in patients with non-alcoholic fatty liver disease: a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver ailment worldwide, in which nonpharmacological strategies have a considerable role in the treatment. Probiotic supplementation as well as physical exercise can improve cardiometabolic parameters, but further research is needed to determine the effects of combined treatment versus exercise alone in managing NAFLD-associated biomarkers, primarily liver enzymes, lipid markers, and insulin resistance. OBJECTIVES: This systematic review and meta-analysis aimed to evaluate the effects of probiotic supplementation, combined with exercise versus exercise alone, on liver enzymes and cardiometabolic markers in patients with NAFLD. METHODS: A systematic review and meta-analysis of randomized clinical trials was performed by searching PubMed, Scopus, and Web of Science databases up to April 2024. The search was restricted to articles published in the English language and human studies. Random effects models were used to calculate weighted mean differences (WMD). RESULTS: Pooled estimates (9 studies, 615 patients, intervention durations ranging from 8 to 48 weeks) revealed that probiotics plus exercise decreased aspartate transaminase (AST) [WMD=-5.64 U/L, p = 0.02], gamma-glutamyl transferase (GGT) [WMD=-7.09 U/L, p = 0.004], low-density lipoprotein (LDL) [WMD=-8.98 mg/dL, p = 0.03], total cholesterol (TC) [WMD=-16.97 mg/dL, p = 0.01], and homeostatic model assessment for insulin resistance (HOMA-IR) [WMD=-0.94, p = 0.005] significantly more than exercise only. However, probiotics plus exercise did not significantly change high-density lipoprotein (HDL) [WMD = 0.07 mg/dL, p = 0.9], fasting insulin [WMD=-1.47 µIU/mL, p = 0.4] or fasting blood glucose (FBG) [WMD=-1.57 mg/dL, p = 0.3] compared with exercise only. While not statistically significant, there were clinically relevant reductions in alanine aminotransferase (ALT) [WMD=-6.78 U/L, p = 0.1], triglycerides (TG) [WMD=-21.84 mg/dL, p = 0.1], and body weight (BW) [WMD=-1.45 kg, p = 0.5] for probiotics plus exercise compared with exercise only. The included studies exhibited significant heterogeneity for AST (I2 = 78.99%, p = 0.001), GGT (I2 = 73.87%, p = 0.004), LDL (I2 = 62.78%, p = 0.02), TC (I2 = 72.41%, p = 0.003), HOMA-IR (I2 = 93.86%, p = 0.001), HDL (I2 = 0.00%, p = 0.9), FBG (I2 = 66.30%, p = 0.01), ALT (I2 = 88.08%, p = 0.001), and TG (I2 = 85.46%, p = 0.001). There was no significant heterogeneity among the included studies for BW (I2 = 0.00%, p = 0.9). CONCLUSION: Probiotic supplementation combined with exercise training elicited better results compared to exercise alone on liver enzymes, lipid profile, and insulin resistance in patients with NAFLD. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42023424290.

Effects of intermittent fasting combined with exercise on serum leptin and adiponectin in adults with or without obesity: a systematic review and meta-analysis of randomized clinical trials.

Context: Intermittent fasting (IF) and exercise training (Exe) have been evaluated in several studies for improving cardiometabolic biomarkers related to weight loss. However, further investigation is required to understand the potential effects on leptin and adiponectin concentrations. IF protocols have been shown to be efficient in improving adipokines, but further research is required to determine whether or not IF regimens combined with Exe are superior to Exe alone. Objective: The aim of this study was to determine whether or not interventions combining IF plus Exe are more effective than Exe only for improving serum leptin and adiponectin in adults with and without obesity. Data extraction: A systematic review and meta-analysis was performed by searching PubMed, Scopus, and Web of Science databases up to August 2023 for randomized clinical trials that determined the effects of IF plus Exe vs. Exe alone (control) on body weight, serum leptin, and serum adiponectin. Analyses were conducted for IF plus Exe vs. Exe alone to calculate weighted mean differences (WMD) and standardized mean differences (SMD). Analysis: The current meta-analysis included 6 studies with a total sample of 153 participants, with intervention durations ranging from three days to 52 weeks. IF plus Exe elicited significantly larger decreases in leptin levels [SMD = -0.47, p = 0.03], which were accompanied by weight loss [WMD = -1.25 kg, p = 0.05], as compared with exercise-only interventions, but adiponectin did not differ between the two [SMD = 0.02, p = 0.9]. Conclusion: IF combined with Exe reduced leptin significantly, but did not change adiponectin levels, when compared to exercise only. Perhaps these reductions in leptin levels may have been associated with weight loss; however, due to the small number of included studies and the high heterogeneity in the weight loss outcomes, this result is uncertain. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023460735.

Effects of Streptozotocin Induced Diabetes on One-Carbon Cycle and Sperm Function.

In this article published in Cell J, Vol 26, No 1, 2024, on pages 81-90, the authors found that the affiliation of authors in address 1 and also the two corresponding authors had accidentally missed during the formatting of the paper. Therefore, we corrected them. The authors would like to apologize for any inconvenience.

Effects of low-carbohydrate diets, with and without caloric restriction, on inflammatory markers in adults: a systematic review and meta-analysis of randomized clinical trials.

Low-carbohydrate diets (LCDs) have gained interest due to their favorable effects on health outcomes, such as inflammation. However, further research is needed to ascertain the overall effects of LCDs on inflammatory parameters, but at the same time considering weight loss and calorie intake. Thus, a systematic review and meta-analysis of randomized clinical trials was performed to investigate the effects of LCDs compared with low-fat diets (LFDs), with and without caloric restriction, on inflammatory markers in adults. PubMed, Scopus, and Web of Science were searched through March 2022 to select intervention studies addressing LCDs vs. LFDs, in which the following circulating inflammatory markers were used: C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), and interleukin (IL-6). Analyses were conducted comparing LCDs vs. LFDs through weighted mean differences (WMD) or standardized mean differences (SMD) and 95% confidence intervals (95% CIs) using random effects models. The systematic review and meta-analysis included a total of 51 studies with a total sample of 4,164 adults, with or without other chronic diseases. Intervention durations ranged from 2-144 weeks. LCDs, compared with LFDs, significantly decreased body weight [WMD = -1.35%, p = 0.001], CRP [SMD = -0.1, p = 0.03], and IL-6 [SMD = -0.15, p = 0.09]. However, LCDs did not significantly decrease TNF-α [SMD = -0.02, p = 0.7] compared to LFDs. In conclusion, LCDs have a beneficial effect on markers of inflammation by decreasing CRP and IL-6; this effect has an association with weight loss. However, LCDs were not more effective than LFDs in decreasing TNF-α.

Effects of Streptozotocin Induced Diabetes on One-Carbon Cycle and Sperm Function.

OBJECTIVE: Diabetic men suffer an increased risk of infertility associated with signs of oxidative damage and decreased methylation in sperm pointing to a deficit of the one-carbon cycle (1CC). We aimed to investigate this deficit using mice models (type 1 and 2) of streptozotocin-induced diabetes. MATERIALS AND METHODS: In this experimental study, 50 male mice, aged eight weeks, were divided randomly into four groups: sham, control, type 1 diabetes mellitus (DM1), and DM2. The DM1 group was fed a normal diet (ND) for eight weeks, followed by five consecutive days of intraperitoneal administration of Streptozotocin (STZ, 50 mg/kg body weight). The DM2 group was fed a high-fat diet (HFD) for eight weeks, followed by a single intraperitoneal injection of STZ (100 mg/kg). After twelve weeks, all the mice were euthanized, and study parameters assessed. In the sham group, citrate buffer as an STZ solvent was injected. RESULTS: Both types of diabetic animals had serious impairment of spermatogenesis backed by increased DNA damage (P=0.000) and decreased chromatin methylation (percent: P=0.019; intensity: P=0.001) and maturation (P=0.000). The 1CC was deeply disturbed with increased homocysteine (P=0.000) and decreased availability of carbon units [methionine (P=0.000), serine (P=0.088), folate (P=0.016), B12 (P=0.025)] to feed methylations. CONCLUSION: We have observed a distinct impairment of 1CC within the testes of individuals with diabetes. We speculate that this impairment may be linked to inadequate intracellular glucose and diminished carbon unit supply associated with diabetes. As a result, interventions focusing on enhancing glucose uptake into sperm cells and providing supplementary methyl donors have the potential to improve fertility issues in diabetic patients. However, additional clinical testing is required to validate these hypotheses.

Effects of treadmill training on myelin proteomic markers and cerebellum morphology in a rat model of cuprizone-induced toxic demyelination.

BACKGROUND: Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system (CNS). If demyelination is persistent, it will result in irreversible axonal injury and loss. The purpose of the current study was to investigate the effects of treadmill training on myelin proteomic markers and cerebellum morphology in a rat model of cuprizone-induced toxic demyelination. METHODS: Thirty male rats were randomly assigned to five groups (n = 6 per group), consisting of a healthy control group (Control), a cuprizone (CPZ) group, and three exercise training groups: exercise training before and during the CPZ administration (EX-CPZ-EX), exercise training before the CPZ administration (EX-CPZ), and exercise training during the CPZ administration (CPZ-EX). A rat model of CPZ-induced toxic demyelination consisted of feeding the rats cuprizone pellets (0.2%) for 6 weeks. All exercise groups performed a treadmill training protocol 5 days/week for 6 weeks. Levels of Myelin proteolipid protein (PLP), Myelin oligodendrocyte glycoprotein (MOG), axonal injury in the cerebellar tissue, and volume, weight, and length of the cerebellum were determined. RESULTS: Results indicated a significant decrease in PLP and MOG in the CPZ groups compared to the Control group (****p < 0.0001). There was a significant increase in PLP and MOG and a significant decrease in axonal injury in the EX-CPZ-EX group as compared to other CPZ groups (****p < 0.0001), and CPZ-MS and CPZ-EX were not significantly different from one another. However, there were no significant differences between the groups for the volume, weight, or length of the cerebellum. CONCLUSION: Treadmill training improved myelin sheath structural proteins and axonal injury in cerebellar tissue in a rat model of CPZ-induced toxic demyelination.

Effects of intermittent fasting combined with physical exercise on cardiometabolic outcomes: systematic review and meta-analysis of clinical studies.

CONTEXT: Different intermittent fasting (IF) protocols have been proven to be efficient in improving cardiometabolic markers, but further research is needed to examine whether or not combining IF regimens plus physical exercise is superior to control diets (ie, nonfasting eating) plus physical exercise in this setting. OBJECTIVE: The aim of this study was to determine whether or not combining IF plus exercise interventions is more favorable than a control diet plus exercise for improving cardiometabolic health outcomes. DATA SOURCE: PubMed, Scopus, and Web of Science were comprehensively searched until April 2023. DATA EXTRACTION: Electronic databases were searched for clinical trials that determined the effect of IF plus exercise vs a control diet plus exercise on body weight, lipid profile (high-density lipoprotein [HDL], low-density lipoprotein [LDL], triglycerides, and total cholesterol), and systolic and diastolic blood pressure (SBP and DBP, respectively). Analyses were conducted for IF plus exercise vs a nonfasting diet plus exercise to calculate weighted mean differences (WMDs). DATA ANALYSIS: The meta-analysis included a total of 14 studies, with a total sample of 360 adults with or without obesity. The duration ranged from 4 to 52 weeks. IF plus exercise decreased body weight (WMD = -1.83 kg; P = 0.001), LDL (WMD = -5.35 mg/dL; P = 0.03), and SBP (WMD = -2.99 mm Hg; P = 0.003) significantly more than a control diet plus exercise. HDL (WMD = 1.57 mg/dL; P = 0.4) and total cholesterol (WMD = -2.24 mg/dL; P = 0.3) did not change significantly for IF plus exercise vs a control diet plus exercise, but there was a trend for reducing triglycerides (WMD = -13.13 mg/dL; P = 0.07) and DBP (WMD = 2.13 mm Hg; P = 0.05), which shows clinical magnitude. CONCLUSION: IF plus exercise improved some cardiometabolic outcomes (body weight, blood pressure, and lipid profile) compared with a control diet plus exercise. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42023423878.

The effects of exercise training on insulin resistance in children and adolescents with overweight or obesity: a systematic review and meta-analysis.

Aim: The aim of present meta-analysis was to determine the effects of exercise training (Exe) on insulin resistance (IR) and body weight in children and adolescents with overweight or obesity. Methods: PubMed, Web of Science, and Scopus were searched for original articles, published through October 2022 that included exercise versus control interventions on fasting glucose, insulin, HOMA-IR, and body weight outcomes in children and adolescents with overweight or obesity. Standardized mean differences (SMD) for fasting insulin, and weighted mean differences (WMD) for fasting glucose, HOMA-IR, body weight (BW), and 95% confidence intervals were determined using random effects models. Results: Thirty-five studies comprising 1,550 children and adolescents with overweight and obesity were included in the present meta-analysis. Exercise training reduced fasting glucose (WMD=-2.52 mg/dL, p=0.001), fasting insulin (SMD=-0.77, p=0.001), HOMA-IR (WMD=-0.82, p=0.001), and BW (WMD=-1.51 kg, p=0.001), as compared to a control. Subgroup analyses showed that biological sex, intervention duration, type of exercise training, BMI percentile, and health status (with or without diagnosed condition), were sources of heterogeneity. Conclusion: Exercise training is effective for lowering fasting glucose, fasting insulin, HOMA-IR, and BW in children and adolescents with overweight or obesity and could provide an important strategy for controlling IR and related factors. With clear evidence for the effectiveness of exercise interventions in this vulnerable population, it is important to determine effective approaches for increasing exercise training in children and adolescents with overweight or obesity.

The effects of aerobic exercise on liver function, insulin resistance, and lipid profiles in prediabetic and type 2 diabetic mice.

BACKGROUND AND AIMS: The purpose of the current study was to evaluate the expression of gluconeogenesis and insulin resistance key genes; including insulin receptor substrate 1 (Irs1), a serine/threonine protein kinase (Akt), forkhead box class-O 1 (FoxO1) and phosphoenolpyruvate carboxykinase (Pepck) genes, and lipid profiles following either a standard or a high-fat diet (HFD) and either an aerobic exercise or non-exercise intervention in prediabetic and type 2 diabetic (T2DM) mice. METHODS: 24 male mice were randomly assigned to two groups fed with a normal diet (ND) or a HFD for 12 weeks. The mice in each group were again randomly assigned to two groups to create four groups in total: 1. Prediabetes-exercised (Prediabetes-Exe), 2. Prediabetes-non exercised (Prediabetes-Non exe), 3. Healthy-exercised (Healthy-Exe), and 4. Healthy-non exercised (Healthy-Non exe). Eighteen additional male mice were fed with the HFD for 8 weeks, after which streptozotocin (STZ) was administered. The mice were then fed the HFD for an additional 4 weeks. These T2DM mice were then randomly divided into two groups: 1. Diabetes-exercised (Diabetic-Exe), and 2. Diabetes-Non exe. The three Exe groups all exercised on a treadmill for 8 weeks for 5 sessions/week. After the last training session, liver tissue was extracted, and the expression of Irs1, Akt, FoxO1, and Pepck genes was measured using real time quantitative Polymerase chain reaction tests. Lipid profiles were measured in serum and in the liver. RESULTS: The expression of both Irs1 and Akt was significantly increased in the Healthy-Exe, Prediabetes-Exe, and Diabetes-Exe groups as compared to the Healthy-Non exe, Prediabetes-Non exe, and Diabetes-Non exe groups (p < 0.001). Additionally, the expression of FoxO1 (p < 0.05) and Pepck (p < 0.001) decreased significantly in the Prediabetes-Exe, and Diabetes-Exe groups as compared to the Prediabetes-non exe, and Diabetes-Non exe groups. Aerobic exercise did not lead to reductions in FoxO1 or Pepck expression in the Healthy-Exe mice. CONCLUSIONS: Eight weeks of aerobic exercise (5 sessions/week) significantly increased the expression of key genes that are important for maintaining glucose homeostasis and improving insulin resistance (Irs1 and Akt), and decreased expression of genes that are important for decreasing gluconeogenesis in the liver (FoxO1 and Pepck) in healthy, prediabetic, and T2DM mice. The lipid profiles improved in healthy, prediabetic, and T2DM mice.

Exercise training, dietary intervention, or combined interventions and their effects on lipid profiles in adults with overweight and obesity: A systematic review and meta-analysis of randomized clinical trials.

AIMS: We performed a systematic review and meta-analysis to compare the effects of Ex (exercise training) vs. DI (dietary intervention) vs. combined Ex and DI on total cholesterol (TC), low-density lipoprotein cholesterol (LDL), triglycerides (TG), and high-density lipoprotein cholesterol (HDL) in adults with overweight and obesity. DATA SYNTHESIS: PubMed, Web of Science, and Scopus were searched to identify original articles published until March 2022, using keywords for the categories "exercise training," "dietary intervention," "overweight and obesity," and "randomized." Studies that included lipid profiles as outcomes and performed in adults with body mass indexes (BMIs) ≥ 25 kg/m2 were included. A total of 80 studies involving 4804 adult participants were included in the meta-analysis. Ex was not as effective as DI for reducing TC and TG and was less effective for reducing LDL. In addition, Ex increased HDL to a greater extent than DI. Combined interventions decreased TC, TG, and LDL but did not increase HDL more than Ex alone. Combined interventions failed to reduce TC or LDL but decreased TG and increased HDL more than DI alone. CONCLUSIONS: Our results suggest that the combination of Ex and DI can be more effective than either Ex or DI alone in improving lipid profiles in adults with overweight and obesity.

The impact of high-intensity interval training on vascular function in adults: A systematic review and meta-analysis.

Aim: We performed a systematic review and meta-analysis to investigate the effects of high-intensity interval training (HIIT) compared with moderate-intensity continuous training (MICT) or with no exercise (CON) on vascular function in adults who were free of cardiometabolic diseases and those with cardiometabolic diseases. Methods: A search across three electronic databases including Scopus, PubMed, and Web of Science was conducted through February 2022 to identify the randomized trials evaluating HIIT vs. MICT and/or CON on vascular function as measured using brachial artery flow-mediated dilation (FMD) in adults. Separate analyses were conducted for HIIT vs. MICT and/or CON to calculate weighted mean differences (WMD) and 95% confidence intervals (95% CIs) using random or fixed models. Results: A total of 36 studies involving 1,437 participants who were either free of cardiometabolic diseases or had cardiometabolic diseases were included in the meta-analysis. HIIT effectively increased FMD when compared with MICT [1.59% (95% CI 0.87-2.31), p = 0.001] or CON [3.80% (95% CI 2.58-5.01), p = 0.001]. Subgroup analysis showed that HIIT increased FMD in participants with cardiovascular and metabolic diseases, but not in participants who were free of cardiometabolic diseases. In addition, HIIT effectively increased FMD regardless of age and body mass index. Conclusion: We confirm that HIIT is effective for improving vascular function in individuals with metabolic disorders and cardiovascular diseases and has a superior effect compared to MICT, demonstrating time efficiency. Systematic review registration: [https://www.crd.york.ac.uk/prospero], identifier [CRD42022320863].

The effect of green coffee and/or endurance exercise on sperm function in pre-diabetic mice.

This study aimed to investigate the effect of green coffee (GC), chlorogenic acid (CA) as an active ingredient of GC and exercise, alone or in a combination with exercise, on spermatogenesis and sperm function in pre-diabetic mice. Results revealed that pre-diabetic status can have a significant adverse effect on spermatogenesis (Johnson score), and sperm concentration, motility, DNA damage and persistent histone in compared to the control group. Although lipid peroxidation, intracellular ROS production, and persistent histones in sperm were high in pre-diabetic mice, exercise only can improve sperm motility. GC alone only improved sperm motility in pre-diabetic mice while CA alone, even did not have this beneficial effect. However, GC along with exercise, did not improve motility but reduce DNA damage, while CA with exercise, significantly improved motility compared to pre-diabetic stage and to the level comparable to control. Therefore, based on this result in individuals with high DNA damage, GC supplementation and exercise could be useful approach while in asthenozoospermia, CA supplementation and exercise should be considered as an alternative approach. However, such an interpretation awaits validation.

Noncoding RNAs Associated with PPARs in Etiology of MAFLD as a Novel Approach for Therapeutics Targets.

Background: Metabolic associated fatty liver disease (MAFLD) is a complex disease that results from the accumulation of fat in the liver. MAFLD is directly associated with obesity, insulin resistance, diabetes, and metabolic syndrome. PPARγ ligands, including pioglitazone, are also used in the management of this disease. Noncoding RNAs play a critical role in various diseases such as diabetes, obesity, and liver diseases including MAFLD. However, there is no adequate knowledge about the translation of using these ncRNAs to the clinics, particularly in MAFLD conditions. The aim of this study was to identify ncRNAs in the etiology of MAFLD as a novel approach to the therapeutic targets. Methods: We collected human and mouse MAFLD gene expression datasets available in GEO. We performed pathway enrichment analysis of total mRNAs based on KEGG repository data to screen the most potential pathways in the liver of MAFLD human subjects and mice model, and analyzed pathway interconnections via ClueGO. Finally, we screened disease causality of the MAFLD ncRNAs, which were associated with PPARs, and then discussed the role of revealed ncRNAs in PPAR signaling and MAFLD. Results: We found 127 ncRNAs in MAFLD which 25 out of them were strongly validated before for regulation of PPARs. With a polypharmacology approach, we screened 51 ncRNAs which were causal to a subset of diseases related to MAFLD. Conclusion: This study revealed a subset of ncRNAs that could help in more clear and guided designation of preclinical and clinical studies to verify the therapeutic application of the revealed ncRNAs by manipulating the PPARs molecular mechanism in MAFLD.

Comparative Impact of Various Exercises on Circulating Irisin in Healthy Subjects: A Systematic Review and Network Meta-Analysis.

Irisin is a myokine that is secreted from skeletal muscle during exercise and increases lipid metabolism, converting white adipose tissue to brown adipose tissue. Recent studies have shown conflicting results in relation to chronic and acute exercise and irisin. The aim of this study was to evaluate the effects of chronic and acute exercise training on circulating (plasma/serum) irisin level in healthy subjects. We conducted a search of Cochrane Library, PubMed, ISI, Scopus, Embase, and Pedro up to September 2021. A random effects network meta-analysis was performed to calculate the pooled estimate of standardized mean difference (SMD) for acute and chronic exercise effects on irisin level, using Hedge's g statistic. Of the 16 studies included, six were acute exercise studies (175 participants). The aerobic (Hedge's g = 0.23; 95% CI: -0.58, 1.03) and the anaerobic exercises (Hedge's g = 0.12; 95% CI: -0.45, 0.70) were associated with the increased level of irisin, compared to the control. In the ten chronic exercise studies (433 participants), the resistance training was superior to anaerobic and aerobic training (P score = 0.632). However, comparing acute and chronic exercise studies, acute training showed the most excellent potential as the best treatment to improve the irisin level (P score = 0.721). This network meta-analysis showed that acute aerobic exercise has a more effect on irisin levels than acute anaerobic exercise. Also, chronic resistance training has the greatest additive effect on irisin levels compared to chronic aerobic and anaerobic training.

Insulin-Related Liver Pathways and the Therapeutic Effects of Aerobic Training, Green Coffee, and Chlorogenic Acid Supplementation in Prediabetic Mice.

Background: The liver controls blood glucose levels via regulation of anabolic (glycogen synthesis and gluconeogenesis) and catabolic (glycolysis and glycogenolysis) processes through activation of the PI3K-AKT signalling pathway. The aim of this study was to assess the effect of aerobic training, green coffee, and chlorogenic acid supplementation on glucose metabolism-regulating pathways in prediabetic mice. Methods: C57BL/6 mice were exposed to a high-fat diet and physical activity limitation to induce a state of prediabetes. After 12 weeks, mice were fed a high-fat diet compared to the control mice. The prediabetic mice were further treated with either green coffee, chlorogenic acid, or training or combinations of the same for 10 weeks. At the end of the experimental period, metabolic data (FBG, GTT, HOMA for IR, plasma level of insulinfrom systematic, AST, and ALT assessed into blood), histopathologic, and analysis of gene and protein expressions were obtained for target tissues. Results: Training along with green coffee and chlorogenic acid supplementation improved complications of prediabetes including weight gain and elevated fasting blood glucose and plasma insulin levels. These effects were associated with the changes in mRNA levels of genes important in hepatic glycogen synthesis (GYS2), glucogenesis (PCK and G6PC2), and glycolysis (GK, PK, and PFKL). Conclusion: The training in conjunction with green coffee or chlorogenic acid is effective in the prevention of prediabetes in mice. As these interventions are relatively inexpensive and safe application to individuals with prediabetes appears warranted.

Aerobic exercise modulates noncoding RNA network upstream of FNDC5 in the Gastrocnemius muscle of high-fat-diet-induced obese mice.

The purpose of the study was to determine the influence of aerobic exercise with a fat-rich diet on ncRNAs expression associated with FNDC5 in the Gastrocnemius muscle of the obese mice. Twenty-five male mice were grouped into two categories of normal diet (ND) and high-fat diet (HF) treatments for three months. For the subsequent treatment, HF-fed animals (obese) were proceeded in four groups: HF-Trained (n = 5), HF-Untrained (n = 5), ND-Trained (n = 5), and ND-Untrained (n = 5). Simultaneously, ND fed mice (n = 5) continued receiving normal diet and being untrained. In the training group, exercise was applied using a treadmill for 2 months. The Gastrocnemius muscle was excised for the assessment of FNDC5 mRNA, protein levels, and ncRNAs. Using bioinformatics tools, two potential miRNAs, miR-129-5p and miR-140-5p, and four lncRNAs constructing a network with FNDC5 were identified. Significant decrease was observed in both miR-129-5p and miR-140-5p in the HF-fed mice vs. ND-fed mice (p < 0.01). Significant increase of lncRNAs Meg3, Malat1, Neat1, and Kcnq1ot1 correlating in the network was also detected (p < 0.001 for all lncRNAs) in HF-fed mice and trained mice (p < 0.001 for Neat1, Meg3, and Kcnq1ot1). The present study suggests that an increase in the muscle FNDC5 of the high-fat diet mice is governed by an expression regulation of suggested ncRNAs, which were revealed by bioinformatics study to be involved in the insulin resistance and glucose homeostasis pathways.

Modulation and bioinformatics screening of hepatic mRNA-lncRNAs (HML) network associated with insulin resistance in prediabetic and exercised mice.

BACKGROUND: Insulin resistance is associated with prediabetes and further progression to type 2 diabetes mellitus (T2DM). This study aims to investigate novel hepatic lncRNAs associated with key genes in insulin resistance in prediabetes. METHODS: In the bioinformatics phase, we have collected screened a pool of lncRNAs and mRNAs according to their potential association to prediabetic condition. We performed pathway analysis of mRNAs, using DAVID tool based on KEGG repository data. Then, we used Python programming language to get a subset of lncRNAs located in 50 kb proximity with high-fat (HF)-responsive mRNAs. In the experimental phase, prediabetic mice model was established by the treatment of HF diets for 12 weeks. After this treatment, HF-fed animals were divided into two groups of endurance exercised or sedentary, both continuing on the HF diet for 8 weeks. Besides, a group of diabetic mice was treated using a HF diet for 8 weeks followed by injection with STZ solution and then a HF diet for another 4 weeks. RESULTS: We found three genes having paired lncRNAs annotated in insulin resistance pathway. Their hepatic expression levels were altered in prediabetic condition as upregulation of Srebf1 was associated with GM38501, upregulation of Pck1 was associated with Ctcflos and GM36691, downregulation of Cpt1b was associated with GM44502. All of these expression patterns were replicated in diabetic mice, correlated positively with their predicted lncRNAs. Interestingly, exercise reversed their expression patterns. CONCLUSIONS: We suggest that the expression pattern of the hepatic mRNA-lncRNA (HML) network in prediabetic state undergoes similar modification to that of diabetes.

Effect of aerobic exercise, low-fat and high-fat diet on the testis tissue and sperm parameters in obese and nonobese mice model.

Semen quality and male fertility depend on numerous factors such as age, environment, lifestyle, physical activity, genetic background and occupation. We aimed to access the effect of aerobic exercise, low- and high-fat diet on mice testis tissue, and sperm function. Obese and nonobese male mice C57BL/6 were exposed to high fat (Hf) or low fat (Lf) and/or activity (Exe: exercise or Sed: sedentary). Finally, testicular morphometric characteristics, sperm concentration and motility (light microscopy), sperm morphology (eosin/nigrosin dye), lipid peroxidation (BODIPY C11 Probe), chromatin (acridine orange and chromomycin A3 staining) were compared within obese groups (Hf/Exe, Lf/Exe, Lf/Sed, Hf/Sed) and nonobese groups (Hf/Exe, Lf/Exe, Lf/Sed, Hf/Sed). Both exercise and diet interventions did not show any alteration in testicular morphological characteristics, sperm morphology and DNA fragmentation within both obese and nonobese groups (p > 0.05). Exercise and/or diet resulted in a significant increase in sperm concentration and motility within both groups (p < 0.05). Exercise in both groups leads to high percentage of lipid peroxidation (p < 0.05). Exercise intervention significantly improved sperm protamine deficiency within obese group (p < 0.05). We concluded that exercise intervention was more effective than diet in improvement of sperm function within obese groups.

Comparative studies on the effects of high-fat diet, endurance training and obesity on Ucp1 expression in male C57BL/6 mice.

BACKGROUND: Obesity triggers a variety of severe conditions, therefore deteriorates metabolism rate of adipose tissues and muscles. Uncoupling proteins which are highly stimulated by fatty acids are potential targets for anti-obesity agents through breaking the electron gradient in the mitochondrial matrix and creating imbalances in the electron transport chain, thereby increasing the amount of substrate used to produce energy. Therefore, the aim of present study is assessment of exercise and high fat diet on expression level of Ucp1 subcutaneous white and brown adipose tissues (scWAT & BAT) respectively. METHODS: To perform experiments, 48 male C57BL/6 mice were divided to two major groups and fed with high fat diet (HFD) or low fat diet (LFD) during a period of 12 weeks. After the first intervention, each groups was divided into four groups randomly as (HF-EX), (HF-SED), (LF-EX), (LF-SED) [EX: exercise; SED: sedentary] in form of treadmill running for 45 min/day, 5 days/week during 8 weeks. One day after the last practice session, mice were sacrificed and Ucp1 expression was assessed on scWAT & BAT. RESULTS: Data indicated a down-regulation in scWAT Ucp1 in obese mice similar to what observed for the expression of Pgc1α. Both, BAT Ucp1 and Pgc1α mRNA decreased significantly in response to obesity and physical activity. Moreover, exercise caused significant decrease in scWAT mitochondrial proteins contradictory to BAT. CONCLUSION: Taken together, exercise exerted controversial effects compared with HFD and obesity on expression of Ucp1 and Pgc1α in scWAT dissimilar to BAT tissues, concluding that obesity may cause a resistance to exercise in terms of metabolic demands for scWAT tissue.