Body Glucose Metabolism Research Articles

Impact of exercise intervention with or without curcumin supplementation on body fat composition, glucose, and lipid metabolism in obese adults: A meta‐analysis

Impact of exercise intervention with or without curcumin supplementation on body fat composition, glucose, and lipid metabolism in obese adults: A meta‐analysis

A novel model of cardiovascular–kidney–metabolic syndrome combining unilateral nephrectomy and high-salt–sugar–fat diet in mice

The aim of this study was to explore biological interaction and pathophysiology mechanisms in a new mouse model of cardiovascular–kidney–metabolic (CKM) syndrome, induced by chronic moderate renal failure in combination with consumption of a customized Western diet rich in carbohydrates, fat and salt. Male C57BL/6J mice were subjected to unilateral nephrectomy, fed a customized Western diet rich not only in sugar and fat but also in salt, and followed for 12 weeks or 20 weeks. Sham-operated mice on a standard chow served as healthy controls. Body composition, weight gain, glucose metabolism, fat distribution, blood pressure, cardiac function, vascular reactivity, renal function, inflammation and mitochondrial function were measured and combined with biochemical and histopathological analyses. The novel triple-hit model of CKM syndrome showed signs and symptoms of metabolic syndrome, disturbed glucose metabolism, impaired adipocyte physiology and fat redistribution, cardiovascular dysfunction, renal damage and dysfunction, systemic inflammation, elevated blood pressure and cardiac remodeling. The pathological changes were more pronounced in mice after prolonged exposure for 20 weeks, but no deaths occurred. In the present mouse model of CKM syndrome, profound and significant metabolic, cardiac, vascular and renal dysfunctions and injuries emerged by using a Western diet rich not only in fat and carbohydrates but also in salt. This multisystem disease model could be used for mechanistic studies and the evaluation of new therapeutic strategies.

Low-calorie, high-protein diets, regardless of protein source, improve glucose metabolism and cardiometabolic profiles in subjects with prediabetes or type 2 diabetes and overweight or obesity.

The aim was to study the effect of two low-calorie, high-protein (HP) diets, with most of the protein coming from animal or plant sources, on glycaemic and other cardiometabolic outcomes in subjects with overweight or obesity and glucose metabolism disorders. A total of 117 participants aged >18 years with body mass index over 27.5 kg/m2 and prediabetes or type 2 diabetes mellitus (T2DM) were randomized to one of two HP low-calorie diets (35% of total calories from protein), in which 75% of the protein was from either plant-based sources (HPP) or animal sources (HPA). For both diets, 30% and 35% of the total calories were from fat and carbohydrates, respectively. The dietary intervention lasted 6 months. Both diets improved body composition to a similar extent, including weight loss (-8.05 ± 5.12 kg for the HPA diet and -7.70 ± 5.47 kg for the HPP diet at 6 months) and fat mass, mainly visceral fat. Both diets had a similar beneficial effect on glucose metabolism, including fasting glucose, insulin, homeostasis model assessment of insulin resistance index and glycated haemoglobin. Other biochemical parameters, including lipid profiles, liver enzymes, adipokines and inflammatory biomarkers, similarly improved in both groups. Fasting incretins, mainly glucagon-like peptide 1, decreased significantly in both groups, and this effect correlated with weight loss. Low-calorie HP diets improved body composition, glucose metabolism and other cardiometabolic outcomes, regardless of protein source (either animal or plant sources), in outpatients with prediabetes or T2DM. The clinical trial was registered in ClinicalTrials.gov (identifier: NCT05456347) https://clinicaltrials.gov/study/NCT05456347?term=NCT05456347&rank=1.

Effects of Ginseng Consumption on Cardiovascular HealthBiomarkers in Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Ginseng, with various pharmacological activities, has received increasing attention to improve cardiovascular health (CVH). Therefore, this meta-analysis synthesized the effect of ginseng consumption on biomarkers of CVH in adults. A systematic search was performed in the databases of PubMed, Scopus, Web of Science, Embase, and the Cochrane Library through July 24, 2023 to screen out English-language randomized controlled trials (RCTs) evaluating the effects of ginseng consumption on body composition, blood pressure, vascular stiffness, lipid metabolism, glucose metabolism, insulin resistance, inflammatory cytokines, and adipocytokines in adults. The weighted mean difference (WMD) and 95% confidence interval (CI) were used to evaluate the overall effect size, and STATA 12.0 was used for comprehensive analysis. Forty-five studies were included in the meta-analysis. Ginseng consumption significantly reduced systolic blood pressure (SBP) (WMD = -2.57 mmHg, 95% CI = -4.99 to -0.14, p = 0.038), total cholesterol (TC) (WMD = -4.40 mg/dL, 95% CI = -8.67 to -0.132, p = 0.043), low density lipoprotein cholesterol (LDL-C) (WMD = -2.81 mg/dL, 95% CI = -4.89 to -0.72, p = 0.008), C-reactive protein (CRP) (WMD = -0.41 mg/L, 95% CI = -0.73 to -0.10, p = 0.010), and interleukin-6 (IL-6) (WMD = -2.82 pg./mL, 95% CI = -4.31 to -1.32, p < 0.001). Subgroup analyses suggested that supplementation with ginseng for less than 12 weeks significantly reduced SBP, but 12 weeks or more improved TC and CRP. Ginseng consumption on SBP, TC, and CRP seemed to be more effective on unhealthy participants. The meta-analysis showed that ginseng consumption might have the potential to improve SBP, TC, LDL-C, CRP, and IL-6. These findings suggest that ginseng is a potential candidate for the maintenance of CVH. However, our results had high heterogeneity. Future high-quality studies are needed to firmly establish the clinical efficacy of ginseng consumption.

Body Mass Index and Diabetes Incidence Across the Adult Lifespan: The Baltimore Longitudinal Study of Aging.

Body composition and glucose metabolism change with aging. Whether different levels of body-mass-index (BMI) are needed to define diabetes risk across the adult lifespan is unknown. This work aimed to investigate whether BMI similarly reflects relative fat mass (FM) and diabetes risk across age groups. Participants without diabetes from the Baltimore Longitudinal Study of Aging (973 men, 1073 women), stratified by age (<50, 50-59, 60-69, ≥70 years) and categorized by either World Health Organization (WHO)-defined BMI categories (for normal weight, overweight or obesity) or BMI quartiles. The primary exposure was BMI. The primary outcome was diabetes incidence. The relationship of BMI to dual-energy x-ray absorptiometry-derived FM was also investigated in older vs younger participants. The median (range) follow-up time was 7.1 years (range, 0-29.0 years). Within WHO-defined BMI categories, different age groups demonstrated significantly different FM percentage, FM/lean mass, and waist circumference (P < .05). WHO-defined BMI categories for overweight and obesity were generally related to higher diabetes risk compared to normal weight in all ages except 50 to 59 years. When BMI was categorized by quartiles, diabetes incidence increased dramatically beginning in quartile 2 (23-25 kg/m2) in older groups. BMI cutoffs with equivalent diabetes incidence rate as BMI 25 kg/m2 and 30.0 kg/m2 in individuals younger than 50 years were 22.7 kg/m2 and 25.2 kg/m2 for ages 50 to 59 years; 22.8 kg/m2 and 25.0 kg/m2 for ages 60 to 69 years; and 23.2 kg/m2 and 25.8 kg/m2 for ages 70 years and older, respectively. WHO-defined BMI categories do not reflect similar diabetes risk across the lifespan. Diabetes incidence is greater at lower levels of BMI in older adults and may lead to underestimation of diabetes risk with aging, particularly among those traditionally classified as normal-weight individuals.

The Oldest of Old Male C57B/6J Mice Are Protected from Sarcopenic Obesity: The Possible Role of Skeletal Muscle Protein Kinase B Expression

The impact of aging on body composition and glucose metabolism is not well established in C57BL/6J mice, despite being a common pre-clinical model for aging and metabolic research. The purpose of this study was to examine the effect of advancing age on body composition, in vivo glucose metabolism, and skeletal muscle AKT expression in young (Y: 4 months old, n = 7), old (O: 17–18 months old, n = 10), and very old (VO: 26–27 month old, n = 9) male C57BL/6J mice. Body composition analysis, assessed by nuclear magnetic resonance, demonstrated O mice had a significantly greater fat mass and body fat percentage when compared to Y and VO mice. Furthermore, VO mice had a significantly greater lean body mass than both O and Y mice. We also found that the VO mice had greater AKT protein levels in skeletal muscle compared to O mice, an observation that explains a portion of the increased lean body mass in VO mice. During glucose tolerance (GT) testing, blood glucose values were significantly lower in the VO mice when compared to the Y and O mice. No age-related differences were observed in insulin tolerance (IT). We also assessed the glucose response to AMPK activation by 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR). The change in blood glucose following AICAR administration was significantly reduced in VO mice compared to Y and AG mice. Our findings indicate that lean body mass and AKT2 protein expression in muscle are significantly increased in VO mice compared to O mice. The increase in AKT2 likely plays a role in the greater lean body mass observed in the oldest of old mice. Finally, despite the increased GT, VO mice appear to be resistant to AMPK-mediated glucose uptake.

An Analysis of Age-Related Body Composition Changes and Metabolic Patterns in Korean Adults Using FDG-PET/CT Health Screening Data.

F-18-fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT) can be used to measure bone mineral density (BMD), cross-sectional muscle area (CSMA), Hounsfield units (HU) of liver and muscle, subcutaneous adipose tissue (SAT), abdominal visceral adipose tissue (VAT), and glucose metabolism. The present study aimed to identify age-related changes in body composition and glucose metabolism in Korean using opportunistic FDG-PET/CT imaging. We analyzed FDG-PET/CT, clinical history, and laboratory data abstracted from the medical records of patients who underwent health screening at a single institute between 2017 and 2022. In total, 278 patients were included in the analysis (male:female=140:138). Age and body mass index were positively correlated in female, but negatively correlated in male. BMD decreased with age more in female, and CSMA decreased with age more in male. Muscle HU decreased with age for both sexes. In female, SAT and VAT increased with age; and in male, SAT decreased slightly while VAT remained stable. Muscle glucose metabolism showed no association with age in male but increased with age in female. CSMA correlated positively with BMD overall; and positively correlated with VAT and SAT in male only. In female only, both SAT and VAT showed negative correlations with glucose metabolism and correlated positively with muscle glucose metabolism. Liver HU values were inversely correlated with VAT, especially in female; and positively correlated with muscle glucose metabolism in female only. FDG-PET/CT demonstrated distinct patterns of age-related changes in body composition and glucose metabolism, with significant differences between sexes.

Systemic Health Effects of Oleuropein and Hydroxytyrosol Supplementation: A Systematic Review of Randomized Controlled Trials.

Non-communicable diseases (NCDs) cause 41 million deaths annually, accounting for 74% of global fatalities. The so-called Mediterranean diet, with its especially significant consumption of olive oil, has shown promising results in reducing the risk of developing NCDs, such as cardiovascular, liver, or bone diseases. In the context of the nutritional health benefits of foods, phenolic compounds such as olive oil's main components, oleuropein (OLE) and hydroxytyrosol (HT), have been shown to possess different beneficial effects. However, no systematic review has evaluated the health-promoting effects of OLE and HT until now. Consequently, this systematic review analyzed 12 human randomized controlled trials (RCTs), involving 683 participants, to assess the effects of supplements, pure compounds, or enriched foods containing OLE and HT regarding systemic health outcomes, including CVD risk factors, liver parameters, and bone, joint, and cognitive health. The review found contrasting but encouraging results, with some studies reporting significant modulation of body weight, lipid profile, and glucose metabolism, and improvements in bone, joint, and cognitive functions. The studies described different dosages and forms of supplementation, ranging from 5 mg/d HT to 990 mL/d olive leaf infusion (320.8 mg OLE and 11.9 mg HT), highlighting the need for further research to determine the optimal dosing and duration. Despite the mixed outcomes, OLE and HT supplementation show potential for improving some of the cardiometabolic health outcomes and bone, joint, and cognitive health. However, further studies are necessary to understand their benefits better and address existing limitations.

Long-term metabolic effects of non-nutritive sweeteners

ObjectiveExcessive consumption of added sugars has been linked to the rise in obesity and associated metabolic abnormalities. Non-nutritive sweeteners (NNSs) offer a potential solution to reduce sugar intake, yet their metabolic safety remains debated. This study aimed to systematically assess the long-term metabolic effects of commonly used NNSs under both normal and obesogenic conditions. MethodsTo ensure consistent sweetness level and controlling for the acceptable daily intake (ADI), eight weeks old C57BL/6 male mice were administered with acesulfame K (ace K, 535.25 mg/L), aspartame (411.75 mg/L), sucralose (179.5 mg/L), saccharin (80 mg/L), or steviol glycoside (Reb M, 536.25 mg/L) in the drinking water, on the background of either regular or high-fat diets (in high fat diet 60% of calories from fat). Water or fructose-sweetened water (82.3.gr/L), were used as controls. Anthropometric and metabolic parameters, as well as microbiome composition, were analyzed following 20-weeks of exposure. ResultsUnder a regular chow diet, chronic NNS consumption did not significantly affect body weight, fat mass, or glucose metabolism as compared to water consumption, with aspartame demonstrating decreased glucose tolerance. In diet-induced obesity, NNS exposure did not increase body weight or alter food intake. Exposure to sucralose and Reb M led to improved insulin sensitivity and decreased weight gain. Reb M specifically was associated with increased prevalence of colonic Lachnospiracea bacteria. ConclusionsLong-term consumption of commonly used NNSs does not induce adverse metabolic effects, with Reb M demonstrating a mild improvement in metabolic abnormalities. These findings provide valuable insights into the metabolic impact of different NNSs, aiding in the development of strategies to combat obesity and related metabolic disorders.

Tangzhiping Decoction Improves Glucose and Lipid Metabolism and Exerts Protective Effects Against White Adipose Tissue Dysfunction in Prediabetic Mice.

Prediabetes, characterized by a series of metabolic abnormalities, increases the risk of diabetes and cardiovascular diseases. Tangzhiping (TZP), a clinically validated traditional Chinese medicine formula, is used to treat impaired glucose tolerance. However, the underlying mechanism of TZP in intervening prediabetes is not fully elucidated. The current study aimed to evaluate the protective effect of TZP against prediabetes mice and explore its potential mechanism. After establishing a prediabetic animal model through 12 weeks of high-fat diet (HFD) feeding, mice were subjected to TZP for 8 weeks. Various parameters related to body weight, glucose and lipid metabolism, and insulin sensitivity were measured. Histopathological examinations observed adipose cell size and liver lipid deposition. The Sable Promethion system assessed energy metabolism activity. Transcriptomic analysis of Epididymal white adipose tissue (EWAT) identified enriched pathways and genes. The key genes in the enriched pathways were identified through RT-PCR. Our data revealed that the administration of TZP reduced body weight and fat mass in a prediabetes mouse model. TZP normalized the glucose and insulin levels, improved insulin resistance, and decreased plasma TC and FFA. The alleviation of adipose tissue hypertrophy and lipid deposition by TZP was demonstrated through pathological examination. Indirect calorimetry measurements indicated a potential increase in VO2 and EE levels with TZP. The results of EWAT transcription showed that TZP reversed pathways and genes related to inflammation and catabolic metabolism. RT-PCR demonstrated that the mRNA expression of inflammation and lipolysis, including Tlr2, Ccr5, Ccl9, Itgb2, Lipe, Pnpla2, Cdo1, Ces1d, Echs1, and Acad11, were changed by TZP treatment. TZP effectively alleviates obesity, impaired glucose and lipid metabolism, and insulin resistance. The effect of TZP might be associated with the regulation of gene expression in dysfunctional adipose tissue.

Effects of guanidino acetic acid and betaine supplementation on growth, dietary nutrient digestion and intestinal creatine metabolism in sheep.

The intestine of young ruminants is in the developmental stage and has weaker resistance to the changes of external environment. Improving intestinal health is vital to promoting growth of young ruminants. This study investigated effects of guanidino acetic acid (GAA) and rumen-protected betaine (RPB) supplementation on growth, dietary nutrient digestion and GAA metabolism in the small intestine of sheep. Eighteen healthy Kazakh rams (27.46±0.10kg of body weight and 3-month old) were categorized into control, test group I and test group II, which were fed a basal diet, 1500mg/kg GAA and 1500mg/kg GAA+600mg/kg RPB, respectively. Compared with control group, test group II had increased (p<0.05) average daily gain, plasma creatine level, ether extract (EE) and phosphorus digestibility on day 30. On day 60, the EE apparent digestibility, jugular venous plasma GAA, GAA content in the duodenal mucosa and GAA content in the jejunal and ileal mucosa of test group II were higher (p<0.05) than other groups. Transcriptome analysis revealed that the differentially expressed genes (DEGs) involved in the duodenal pathways of oxidative phosphorylation and non-alcoholic fatty liver disease were significantly altered in test group II versus test group I (p<0.05). Moreover, in the jejunum, the MAPK signalling pathway, complement and coagulation cascade and B-cell receptor signalling pathway were significantly enriched, with ATPase, solute carrier transporter protein, DHFR, SI, GCK, ACACA and FASN being the significantly DEGs (p<0.05). Dietary supplementation of RPB on top of GAA in sheep diets may promote sheep growth and development by improving the body's energy, amino acid, glucose and lipid metabolism capacity.

Characterization of the effects of cannabinoid receptor deletion on energy metabolism in female C57BL mice.

Despite the evidence that energy balance is regulated differently in females and that the endocannabinoid system is sexually dimorphic, previous studies on the endocannabinoid system and energy balance predominantly used male models. Here, we characterize the effects of cannabinoid receptor deletion on body weight gain and glucose metabolism in female C57BL mice. Female mice lacking the cannabinoid-1 receptor (CB1R-/-), cannabinoid-2 receptor (CB2R-/-), or both receptors (CB1R-/-/CB2R-/-) and wild-type (WT) mice were fed with a low (LFD; 10% of calories from fat) or high-fat diet (HFD; 45% of calories from fat) for six weeks. Female WT mice fed with HFD gained significantly more weight than WT mice fed with LFD (p < 0.001). Similar pattern was observed for CB2/- mice fed with HFD compared to CB2R-/- mice fed with LFD (p < 0.001), but not for CB1R-/- fed with HFD vs. LFD (p = 0.22) or CB1R-/-/CB2R-/- fed with HFD vs. LFD (p = 0.96). Comparing the 4 groups on LFD, weight gain of CB1R-/- mice was greater than all other genotypes (p < 0.05). When fed with HFD, the deletion of CB1R alone in females did not attenuate weight gain compared to WT mice (p = 0.72). Female CB1R-/-/CB2R-/- mice gained less weight than WT mice when fed with HFD (p = 0.007) despite similar food intake and locomotor activity, potentially owing to enhanced thermogenesis in the white adipose tissue. No significant difference in weight gain was observed for female CB2R-/- and WT mice on LFD or HFD. Fasting glucose, however, was higher in CB2R-/- mice fed with LFD than all other groups (p < 0.05). The effects of cannabinoid receptor deletion on glucose metabolism in female mice were similar to previously published findings on male mice, yet the effects on body weight gain and thermogenesis were attenuated in CB1R-/- mice.

404-P: Characterization of the Differential Effects of Oxyntomodulin (GLP-1/Glucagon) and GLP-1 on Body Weight, Glucose Metabolism and Renal Function in db/db Mice

404-P: Characterization of the Differential Effects of Oxyntomodulin (GLP-1/Glucagon) and GLP-1 on Body Weight, Glucose Metabolism and Renal Function in db/db Mice

Lipid-encapsulated mRNA encoding an extended serum half-life interleukin-22 ameliorates metabolic disease in mice

ObjectiveInterleukin (IL)-22 is a potential therapeutic protein for the treatment of metabolic diseases such as obesity, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease due to its involvement in multiple cellular pathways and observed hepatoprotective effects. The short serum half-life of IL-22 has previously limited its use in clinical applications; however, the development of mRNA-lipid nanoparticle (LNP) technology offers a novel therapeutic approach that uses a host-generated IL-22 fusion protein. In the present study, the effects of administration of an mRNA-LNP encoding IL-22 on metabolic disease parameters was investigated in various mouse models. MethodsC57BL/6NCrl mice were used to confirm mouse serum albumin (MSA)-IL-22 protein expression prior to assessments in C57BL/6NTac and CETP/ApoB transgenic mouse models of metabolic disease. Mice were fed either regular chow or a modified amylin liver nonalcoholic steatohepatitis–inducing diet prior to receiving either LNP-encapsulated MSA-IL-22 or MSA mRNA via intravenous or intramuscular injection. Metabolic markers were monitored for the duration of the experiments, and postmortem histology assessment and analysis of metabolic gene expression pathways were performed. ResultsMSA-IL-22 was detectable for ≥8 days following administration. Improvements in body weight, lipid metabolism, glucose metabolism, and lipogenic and fibrotic marker gene expression in the liver were observed in the MSA-IL-22–treated mice, and these effects were shown to be durable. ConclusionsThese results support the application of mRNA-encoded IL-22 as a promising treatment strategy for metabolic syndrome and associated comorbidities in human populations.

Do polyphenols affect body fat and/or glucose metabolism?

Obesity is reaching epidemic proportions with 51% of the population expected to be obese by 2030. Recently, polyphenols have been highlighted as an effective approach to managing obesity and associated risks. Polyphenols are a large class of bioactive plant compounds classified into two major categories: flavonoids which are distinguished by the fundamental C6-C3-C6 skeleton and non-flavonoids. This systematic review evaluated the effect of different polyphenol sources in overweight and obese people with and without type 2 diabetes. The primary outcome was lipid profile and the secondary outcomes were blood glucose, HbA1c (%), HOMA-IR, weight, and body mass index. A search was undertaken in PubMed, Web of Science, Medline, and Wiley for randomized control trials that assessed different sources of polyphenols in overweight and obese people with or without type 2 diabetes. The quality of the included studies was assessed using the National Heart, Lung, and Blood Institute Quality Assessment Tool. The search yielded 935 studies, of which six randomized control trials met the inclusion criteria. Five studies found no significant difference in lipid profile between the control and intervention groups in triglycerides, total cholesterol, LDL cholesterol, and HDL cholesterol. However, one study showed significant differences in triglycerides (p = 0.04) and HDL cholesterol (p = 0.05) between the two groups with no significant difference in total cholesterol and LDL cholesterol. There were no significant changes in blood glucose observed in the included studies, with only two studies reporting a significant difference in A1c between the groups. Four studies found no difference in HOMA-IR, while one study showed a significant decrease in HOMA-IR in the intervention group compared to the control group. Three studies reported no difference in BMI or weight between the two groups. The data associated with the specific health benefits of polyphenols and their sources in people with overweight, obese, and type 2 diabetes are still limited, so further research is required to support their use and prove their benefits.

Protocol of the HARMONY study: A culturally relevant, randomized-controlled, stress management intervention to reduce cardiometabolic risk in African American women

BackgroundAfrican American Women (AAW) are at high risk for stress-related cardiometabolic (CM) conditions including obesity, heart disease, and diabetes. Prior interventions lack attention to culturally-nuanced stress phenomena (Superwoman Schema [SWS], contextualized stress, and network stress), which are positively and significantly associated with unhealthy eating and sedentary behavior. PurposeThe HARMONY Study is designed to test a culturally tailored mindfulness-based stress management intervention to address SWS, contextualized stress, and network stress as potential barriers to adherence to healthy exercise and eating goals. The study will help AAW build on their strengths to promote cardiometabolic health by enhancing positive reappraisal, self-regulation, and self-efficacy as protective factors against chronic stress-inducing biobehavioral morbidity and mortality risk. MethodsThis two-arm, randomized-controlled trial will test the effects of two group-based, online interventions. HARMONY 1 includes culturally-tailored exercise and nutrition education. HARMONY 2 includes mindfulness-based stress reduction, exercise, and nutrition education. We aim to recruit 200 AAW ≥ 18 years old with CM risk. ResultsPrimary outcomes (actigraphy and carotenoid levels) and secondary outcomes (body composition, inflammatory markers, glucose metabolism, and stress) are being collected at baseline and 4-, 8-, and 12-months post-intervention. Intent-to-treat, data analytic approaches will be used to test group differences for the primary outcomes. DiscussionThis study is the first to address culturally-nuanced stress phenomena in AAW (SWS, network stress, and contextualized stress) using culturally-tailored stress management, exercise, and nutrition educational approaches to reduce biobehavioral CM risk among AAW. Quantitative and qualitative results will inform the development of scalable and sustainable CM risk-reduction programming for AAW. Trial registrationThe Multiple PIs registered the clinical trial (Identifier: NCT04705779) and reporting of summary results in ClinicalTrials.gov in accordance with the NIH Policy on the Dissemination of NIH-Funded Clinical Trial Information, within the required timelines.

#1131 Significant reno-cardio-metabolic protection by the food additive Flexovital in a murine model combining unilateral nephrectomy and Western diet

Abstract Background and Aims Cardiovascular complications are major threats in advanced renal failure and metabolic dysfunction with several unmet medical needs. This study aimed to investigate the therapeutic effects of a special food additive (FLEXOVITAL) in a newly developed mouse model of reno-cardio-metabolic disease, induced by moderate renal failure in combination with a special Western diet. Method Male C57BL/6J mice (4 weeks old, n = 18) were subject to unilateral nephrectomy (UNX), fed a Western diet rich in fat carbohydrates and salt (WD), and were followed for 12 weeks compared with SHAM-operated mice on standard chow (n = 19). One group of UNX+WD mice (n = 8) was fed a food additive (FLEXOVITAL; FLX) containing extracts of Rhodiola rosea, beetroot, and the amino acids arginine and citrulline. Body weight (BW), blood pressure (tail-cuff), endothelial-dependent vasorelaxation (myograph), glucose metabolism (IPGTT), body fat and lean mass composition (DEXA), adipocyte area, renal function (Glomerular Filtration Rate (GFR) by plasma clearance of FITC-inulin), and mitochondrial function (Oroboros, High-resolution respirometry) were measured together with biochemical analysis of heart injury (Troponin-I), inflammation (IL6) and histological analyses of the kidney and heart. Results BW gain was seen in the UNX+WD and SHAM group, and was 25% less in the FLX group (p &amp;lt; 0.05). The fat/lean-mass ratio increased by 17% (p &amp;lt; 0.01) and the adipocyte area by 31% (p &amp;lt; 0.001) in the UNX+WD group but was virtually normalized in the FLX group (p &amp;lt; 0.01). Fasting and non-fasting glucose levels became elevated in the UNX+WD group and were reduced in the FLX group (p &amp;lt; 0.05). Impaired glucose clearance in the UNX+WD group, was partially prevented by FLX. BP significantly increased in the UNX+WD group (MAP = 78 → 90 mmHg, p &amp;lt; 0.001), and was largely prevented by FLX (MAP = 82 mmHg, p &amp;lt; 0.01). Endothelial function was significantly impaired in the UNX+WD group (p &amp;lt; 0.01) and partially preserved in the FLX group (p &amp;lt; 0.05). GFR was reduced by almost 60% in the UNX+WD group but improved with a 75% protective effect in the FLX group (p &amp;lt; 0.05). Significant glomerular injuries with mesangial proliferation were observed in the UNX+WD group (p &amp;lt; 0.001) but were less pronounced in the FLX group (p &amp;lt; 0.01). Tubular injury score (1-10) increased from 1 in SHAM to 6.5 in the UNX+WD group and was partly protected (4.5) in the FLX group (p &amp;lt; 0.05). Troponin-I levels were 15 pg/ml in the SHAM group, markedly increased in the UNX+WD group (p &amp;lt; 0.001), whereas completely reversed in the FLX group (p &amp;lt; 0.01). No significant histological cardiac injuries or deviations could be demonstrated. Inflammatory activity (IL6) increased by 88% in the UNX+WD there was a trend of reduction in mice with FLX. Mitochondrial oxygen efficiency (P/O ratio) was improved in the kidneys of the FLX group compared to the UNX+WD group (p &amp;lt; 0.05). Conclusion In the present multiorgan disease model, significant renal, cardiovascular, and metabolic dysfunction/injuries emerge in mice with a moderate reduction of renal function when fed a Western diet rich in fat, carbohydrates, and salt. Protective effects were noted by dietary FLX treatment in most functional assessments made in the model. This indicates FLX is a potential new treatment in patients with reno-cardio-metabolic disease. The next phase involves confirming these findings in the clinical setting.

Beneficial effects of time-restricted fasting on cardiovascular disease risk factors: a meta-analysis

BackgroundCardiovascular disease continues to be a leading cause of mortality worldwide, highlighting the need to explore innovative approaches to improve cardiovascular health outcomes. Time-restricted fasting (TRF) is a dietary intervention that involves limiting the time window for food consumption. It has gained attention for its potential benefits on metabolic health and weight management. This study aims to investigate the impact of TRF on key risk factors, including body weight, glucose metabolism, blood pressure, and lipid profile.MethodsWe conducted a systematic search in five databases (Scopus, Embase, PubMed, Cochrane, and Web of Science) for relevant studies up to January 2023. After applying inclusion criteria, 12 studies were eligible for analysis. Quality assessment was conducted using the ROB-2.0 tool and ROBINS-I. Risk of bias was mapped using Revman 5.3, and data analysis included Hartung-Knapp adjustment using R 4.2.2.ResultsThe group that underwent the TRF intervention exhibited a significant decrease in body weight (SMD: -0.22; 95%CI: -0.41, -0.04; P < 0.05) and fat mass (SMD: -0.19; 95%CI: -0.36, -0.02; P < 0.05), while maintaining lean mass (SMD: -0.09; 95%CI: -0.08, 0.26; P > 0.05).ConclusionTRF has shown potential as a treatment strategy for reducing total body weight by targeting adipose tissue, with potential improvements in cardiometabolic function.

The first MASH drug therapy on the horizon: Current perspectives of resmetirom.

The rising prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) poses a significant global health challenge, affecting over 30% of adults worldwide. MASLD is linked to increased mortality rates and substantial healthcare costs, primarily driven by its progression to metabolic dysfunction-associated steatohepatitis (MASH), which can lead to severe liver complications including cirrhosis and hepatocellular carcinoma. Despite its growing burden, effective pharmacotherapy for MASLD/MASH has been lacking until the recent conditional approval of resmetirom by the FDA. Resmetirom, a liver-targeted thyroid hormone receptor-β selective drug, has shown promise in clinical trials for treating non-cirrhotic MASH with moderate to advanced fibrosis. It has demonstrated efficacy in reducing hepatic fat content, improving liver histology (both MASH resolution and fibrosis improvement), and ameliorating biomarkers of liver damage without significant effects on body weight or glucose metabolism. Notably, resmetirom also exhibits favourable effects on circulating lipids, potentially reducing cardiovascular risk in MASLD/MASH patients. The safety profile of resmetirom appears acceptable, with gastrointestinal adverse events being the most common, though generally mild or moderate. However, long-term surveillance is warranted to monitor for potential risks related to thyroid, gonadal, or bone diseases. Clinical implementation of resmetirom faces challenges in patient selection and monitoring treatment response, and will heavily rely on non-invasive tests for liver fibrosis assessment. Nonetheless, resmetirom represents a landmark breakthrough in MASLD/MASH treatment, paving the way for future therapeutic strategies aiming to mitigate the multifaceted risks associated with this complex metabolic liver disease.

Alterations of whole body glucose metabolism in a feline SARS-CoV-2 infection model.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been especially devastating to patients with comorbidities, including metabolic and cardiovascular diseases. Elevated blood glucose during SARS-CoV-2 infection increased mortality of patients with COVID-19, although the mechanisms are not well understood. It has been previously demonstrated that glucose transport and utilization is a crucial pathway for other highly infectious RNA viruses. Thus, we hypothesized that SARS-CoV-2 infection could lead to alterations in cellular and whole body glucose metabolism. Specific pathogen-free domestic cats were intratracheally inoculated with USA-WA1/2020 (wild-type) SARS-CoV-2 or vehicle-inoculated, then euthanized at 4- and 8-days postinoculation (dpi). Blood glucose and cortisol concentrations were elevated at 4 and 8 dpi. Blood ketones, insulin, and angiotensin II concentrations remained unchanged throughout the experimental timeline. SARS-CoV-2 RNA was detected in the lung and heart, without changes in angiotensin-converting enzyme 2 (ACE2) RNA expression. In the lung, SARS-CoV-2 infection increased glucose transporter 1 (GLUT1) protein levels at 4 and 8 dpi, whereas GLUT4 level was only upregulated at 8 dpi. In the heart, GLUT-1 and -4 protein levels remained unchanged. Furthermore, GLUT1 level was upregulated in the skeletal muscle at 8 dpi, and AMPK was activated in the hearts of infected cats. SARS-CoV-2 infection increased blood glucose concentration and pulmonary GLUT protein levels. These findings suggest that SARS-CoV-2 infection induces metabolic reprogramming primarily in the lung to support viral replication. Furthermore, this translational feline model mimicked human COVID-19 and could be used to explore novel therapeutic targets to treat metabolic disease during SARS-CoV-2 infection.NEW & NOTEWORTHY Our study on a feline model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, mirroring human COVID-19, revealed alterations in whole body and cellular glucose metabolism. Infected cats developed mild hyperglycemia, increased protein levels of glucose transporters in the lung, and AMPK activation in the heart. These findings suggest that SARS-CoV-2 infection induces metabolic reprogramming in the cardiorespiratory system to support viral replication. Understanding these mechanisms could lead to novel antiviral therapeutic strategies.