Prevalence Of Metabolic Diseases Research Articles

Ångstrom-scale gold particles loaded with alendronate via alpha-lipoic acid alleviate bone loss in osteoporotic mice

Osteoporosis is a highly prevalent metabolic disease characterized by low systemic bone mass and deterioration of bone microarchitecture, resulting in reduced bone strength and increased fracture risk. Current treatment options for osteoporosis are limited by factors such as efficacy, cost, availability, side effects, and acceptability to patients. Gold nanoparticles show promise as an emerging osteoporosis therapy due to their osteogenic effects and ability to allow therapeutic delivery but have inherent constraints, such as low specificity and the potential for heavy metal accumulation in the body. This study reports the synthesis of ultrasmall gold particles almost reaching the Ångstrom (Ång) dimension. The antioxidant alpha-lipoic acid (LA) is used as a dispersant and stabilizer to coat Ångstrom-scale gold particles (AuÅPs). Alendronate (AL), an amino-bisphosphonate commonly used in drug therapy for osteoporosis, is conjugated through LA to the surface of AuÅPs, allowing targeted delivery to bone and enhancing antiresorptive therapeutic effects. In this study, alendronate-loaded Ångstrom-scale gold particles (AuÅPs-AL) were used for the first time to promote osteogenesis and alleviate bone loss through regulation of the WNT signaling pathway, as shown through in vitro tests. The in vivo therapeutic effects of AuÅPs-AL were demonstrated in an established osteoporosis mouse model. The results of Micro-computed Tomography, histology, and tartrate-resistant acid phosphatase staining indicated that AuÅPs-AL significantly improved bone density and prevented bone loss, with no evidence of nanoparticle-associated toxicity. These findings suggest the possible future application of AuÅPs-AL in osteoporosis therapy and point to the potential of developing new approaches for treating metabolic bone diseases using Ångstrom-scale gold particles.

The Association of Malnutrition and Health-Related Factors among 474,467 Older Community-Dwellers: A Population-Based Data Mining Study in Guangzhou, China.

This study aimed to examine the prevalence and associated factors of malnutrition in older community-dwellers and explore the interaction between associated factors. A total of 474,467 older community-dwellers aged 65 or above were selected in Guangzhou, China. We used a two-step methodology to detect the associated factors of malnutrition and constructed logistic regression models to explore the influencing factors and interactive effects on three patterns of malnutrition. The prevalence of malnutrition was 22.28%. Older adults with both hypertension and diabetes (RERI = 0.13), both meat or fish diet and hypertension (RERI = 0.79), and both meat or fish diet and diabetes (RERI = 0.81) had positive additive interaction effects on the risk of obesity, whereas those on a vegetarian diet with hypertension (RERI = -0.25) or diabetes (RERI = -0.19) had negative additive interaction effects. Moreover, the interactions of physical activity with a meat or fish diet (RERI = -0.84) or dyslipidemia (RERI = -0.09) could lower the risk of obesity. Malnutrition was influenced by different health factors, and there were interactions between these influencing factors. Pertinent dietary instruction should be given according to different nutritional status indexes and the prevalence of metabolic diseases to avoid the occurrences of malnutrition among older adults.

Familial hypercholesterolemia-Plus: is the metabolic syndrome changing the clinical picture of familial hypercholesterolemia?

The purpose of this review article was to describe recent advances in our knowledge about how diabetes and metabolic syndrome are changing the face of familial hypercholesterolemia. Heterozygous familial hypercholesterolemia, most commonly caused by disruption to LDL receptor function, leads to lifelong elevation of LDL cholesterol and increased risk of atherosclerotic cardiovascular disease. Familial hypercholesterolemia was originally described as a form of 'pure' hypercholesterolemia, in the sense that levels of LDL were uniquely affected. Studies of familial hypercholesterolemia among individuals of predominantly Western European descent conformed to the perception that individuals with familial hypercholesterolemia tended to be lean and otherwise metabolically healthy. More recently, as we have studied familial hypercholesterolemia in more diverse global populations, we have learned that in some regions, rates of diabetes and obesity among familial hypercholesterolemia patients are very high, mirroring the global increases in the prevalence of metabolic disease. When diabetes and metabolic disease coexist, they amplify the cardiovascular risk in familial hypercholesterolemia, and may require more aggressive treatment.

Pectolinarigenin ameliorates osteoporosis via enhancing Wnt signaling cascade in PPARβ-dependent manner

BackgroundOsteoporosis is a prevalent metabolic bone disease in older adults. Peroxisome proliferator-activated receptor β (PPARβ), the most abundant PPAR isotype expressed in bone tissues, plays a critical role in regulating the energy metabolism of osteoblasts. However, the botanical compounds targeting PPARβ for the treatment of osteoporosis remain largely unexplored. PurposeTo discover a potent PPARβ agonist from botanical compounds, as well as to investigate the anti-osteoporosis effects and to elucidate the underlying mechanisms of the newly identified PPARβ agonist. MethodsThe PPARβ agonist effects of botanical compounds were screened by an in vitro luciferase reporter gene assay. The PPARβ agonist effects of pectolinarigenin (PEC) in bone marrow mesenchymal stromal cells (BMSCs) were validated by Western blotting. RNA-seq transcriptome analyses were conducted to reveal the underlying osteoporosis mechanisms of PEC in BMSCs. The PPARβ antagonist (GSK0660) and Wnt signaling inhibitor (XAV969) were used to explore the role of the PPARβ and Wnt signaling cascade in the anti-osteoporosis effects of PEC. PEC or the PEG-PLGA nanoparticles of PEC (PEC–NP) were intraperitoneally administrated in both wild-type mice and ovariectomy-induced osteoporosis mice to examine its anti-osteoporotic effects in vivo. ResultsPEC, a newly identified naturally occurring PPARβ agonist, significantly promotes osteogenic differentiation and up-regulates the osteogenic differentiation-related genes (Runx2, Osterix, and Bmp2) in BMSCs. RNA sequencing and functional gene enrichment analysis suggested that PEC could activate osteogenic-related signaling pathways, including Wnt and PPAR signaling pathways. Further investigations suggested that PEC could enhance Wnt/β-catenin signaling in a PPARβ-dependent manner in BMSCs. Animal tests showed that PEC–NP promoted bone mass and density, increased the bone cell matrix protein, and accelerated bone formation in wild-type mice, while PEC–NP also played a preventive role in ovariectomy-induced osteoporosis mice via maintaining the expression level of bone cell matrix protein, balancing the rate of bone formation, and slowing down bone loss. Additionally, PEC–NP did not cause any organ injury and body weight loss after long-term use (11 weeks). ConclusionPEC significantly promotes bone formation and reduces bone loss in both BMSCs and ovariectomy-induced osteoporosis mice via enhancing the Wnt signaling cascade in a PPARβ-dependent manner, providing a new alternative therapy for preventing estrogen deficiency-induced osteoporotic diseases.

Probiotic Mixture Ameliorates a Diet-Induced MASLD/MASH Murine Model through the Regulation of Hepatic Lipid Metabolism and the Gut Microbiome.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent metabolic disease that has no effective treatment. Our proprietary probiotic mixture, Prohep, has been proven in a previous study to be helpful in reducing hepatocellular carcinoma (HCC) in vivo. However, its prospective benefits on the treatment of other liver diseases such as MASLD, which is one of the major risk factors in the development of HCC, are unclear. To investigate the potential of Prohep in modulating the development and progression of MASLD, we first explored the effect of Prohep supplementation via voluntary intake in a high-fat diet (HFD)-induced MASLD/metabolic dysfunction-associated steatohepatitis (MASH) murine model. Our results indicated that Prohep alleviated HFD-induced liver steatosis and reduced excessive hepatic lipid accumulation and improved the plasma lipid profile when compared with HFD-fed control mice through suppressing hepatic de novo lipogenesis and cholesterol biosynthesis gene expressions. In addition, Prohep was able to modulate the gut microbiome, modify the bile acid (BA) profile, and elevate fecal short-chain fatty acid (SCFA) levels. Next, in a prolonged HFD-feeding MASLD/MASH model, we observed the effectiveness of Prohep in preventing the transition from MASLD to MASH via amelioration in hepatic steatosis, inflammation, and fibrosis. Taken together, Prohep could ameliorate HFD-induced MASLD and control the MASLD-to-MASH progression in mice. Our findings provide distinctive insights into the development of novel microbial therapy for the management of MASLD and MASH.

Abstract 2190: Transcriptomic signatures of obesity-driven colon cancer: A multi-species transdisciplinary approach

Abstract Obesity is a highly prevalent metabolic disease and an established risk factor for colon cancer. However, critical biological pathways underpinning this relationship remain undetermined. Herein, we integrate human and murine colon tumor transcriptomic data to identify obesity-responsive pathways conserved between species. Human colon cancer samples (n=155) were collected as part of the clinical ColoCare Study, a prospective cohort study of patients newly diagnosed with colorectal cancer. Enrolled patients were diagnosed with stage I-III colon cancer and treatment naïve at time of tissue collection. Patients were classified as having a BMI <30 kg/m2 (i.e., non-obese) or BMI ≥30 kg/m2 (i.e., obese) at baseline. Age, sex, tumor stage, and collection site were adjusted for in all analyses. Patients were 63.3 ± 13.7 years, 51% male, and 34% had a BMI ≥30. C57BL/6J adult female mice were fed a low-fat control diet (Research Diets D12450J, n= 8) or a high-fat diet-induced obesity regimen (D12492, n=7) for ~23 weeks, at which time 700 Apc-null;KrasG12D/+;Trp53-null;Smad4-null;tdTomato (i.e., AKPS) organoids were orthotopically transplanted into the colonic submucosa via colonoscopy-guided injection. Obese mice weighed more than controls (controls 26.4 ± 3.7 g vs. DIO 45.9 ± 9.7 g) and had more mesenteric fat surrounding the colon (controls 201 ± 143 mg vs. 1176 ± 589 mg). Tumors were excised after 4 weeks of growth. RNA was extracted from bulk human tumor samples and from the epithelial-enriched EpCAM+ cell population in murine tumor samples for RNA sequencing. Genes differentially expressed between the reference and obese groups were identified using DESeq2. For gene set enrichment analysis, genes were preranked by log2 fold change for both human and mouse datasets. There were 76 and 132 differentially expressed genes (DEGs; FDRq<0.10) identified in the human and mouse datasets, respectively. None of these 208 DEGs were common to both datasets. Thirty-five Hallmark gene sets in the human dataset and 25 Hallmark gene sets in the mouse dataset were significantly enriched in the obese group; 18 of these gene sets were common to both mouse and human datasets. These overlapping pathways were largely related to inflammation (e.g., inflammatory response, IL6 JAK STAT3 signaling, TNFɑ signaling) and metabolism (e.g., cholesterol homeostasis, glycolysis, and fatty acid metabolism). Additional analysis revealed 204 genes common between the leading edges of both transcriptomic datasets. These transdisciplinary data suggest that obesity induces a set of metabolic and inflammatory processes and/or pathways in colon tumors which is conserved between mice and humans. Future studies will mechanistically evaluate the role of candidate genes and pathways in obesity-associated colorectal carcinogenesis in our AKPS orthotopic organoid transplant mouse model. Citation Format: Elaine M. Glenny, Tengda Lin, Victoria M. Bandera, Biljana Gigic, Aik Choon Tan, Babak Mirminachi, Saratchandra S. Khumukcham, Alessandro Carpanese, Christy A. Warby, Olena Aksonova, Caroline Himbert, Jennifer Ose, Chris Stubben, David Nix, Kenneth Boucher, Peter Schirmacher, Ildiko Strehli, Jolanta Jedrzkiewicz, Alexander Brobeil, Martin A. Schneider, Christoph Kahlert, Erin M. Siegel, Adetunji T. Toriola, David Shibata, Christopher I. Li, Jane C. Figueiredo, Jatin Roper, Cornelia M. Ulrich, Stephen D. Hursting. Transcriptomic signatures of obesity-driven colon cancer: A multi-species transdisciplinary approach [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2190.

Abstract 2189: Tirzepatide mitigates obesity-associated metabolic dysregulation and tumor progression in a mouse model of triple-negative breast cancer

Abstract Obesity is an established risk factor for breast cancer. Dietary and surgical weight loss interventions reduce breast cancer risk but have significant limitations to their widespread use as anticancer strategies. Incretin-based pharmaceuticals safely and effectively promote weight loss, but whether these drugs exert similar protective effects against cancer is unknown. Here we test whether weight loss induced by the glucagon-like peptide 1 (GLP-1)/glucose-dependent insulinotropic polypeptide (GIP) receptor agonist tirzepatide limits tumor growth in an orthotopic mouse model of triple-negative breast cancer. Ten-week-old female C57BL/6NCrl mice were randomized to either a 10 kcal% low-fat diet (control; n=14) or 60 kcal% high-fat diet to promote diet-induced obesity (DIO; n=43). After 18 weeks on diet, DIO mice were randomized by body weight to either i) remain on the high-fat diet (DIO; n=15); ii) lose weight with tirzepatide (TZP; n=13); or iii) lose weight with 30% daily calorie restriction relative to control mice (CR; n=15). All mice were subcutaneously injected with either TZP or vehicle every other day for 13 weeks with the following escalating dosing schedule: 3 nmol/kg TZP in week 1; 10 nmol/kg TZP in weeks 2-3; 20 nmol/kg TZP in weeks 4-7; 30 nmol/kg TZP in weeks 8-11; and 40 nmol/kg TZP in weeks 12-13. Fasting blood glucose and body composition was assessed after 9 weeks of weight loss, and 35,000 E0771 cells were orthotopically transplanted into the 4th mammary fat pad. Tumors growth was monitored for 4 weeks. TZP-treated mice lost on average >20% weight loss by week 4 and remained at or below 20% weight loss for the remainder of the study. Directly prior to E0771 tumor cell injections, TZP-treated mice had lost 23.6±8.9% body weight, versus 39.7±3.6% in CR mice. Relative to DIO mice, blood glucose control was restored in both weight loss groups (DIO: 149.5±18.5 mg/dl; TZP: 124.5±15.5 mg/dl; CR: 107.6±18.8 mg/dl) and >87.5% of the lost weight was attributed to fat mass, rather than lean mass, for TZP-treated and CR mice. Notably, tirzepatide suppressed tumor growth relative to DIO, but the CR group had a greater anticancer effect than TZP. Reduced tumor mass in both weight loss groups was accompanied by a significant reduction in circulating IGF-1, insulin, and leptin relative to DIO mice. These findings are timely and important because i) obesity is a highly prevalent metabolic disease that increases risk and progression of breast cancer and >13 other cancers; ii) incretin therapies, which show promise as highly effective weight loss drugs, are increasingly being prescribed; and iii) the tumor suppressive effects of tirzepatide described herein newly suggest incretin agonism as another propitious option for breaking the obesity-cancer link. Citation Format: Elaine M. Glenny, Alyssa N. Ho, Violet A. Kiesel, Fangxin Chen, Claire E. Gates, Evan M. Paules, Ruihan Xu, C. Alex Holt, Michael F. Coleman, Stephen D. Hursting. Tirzepatide mitigates obesity-associated metabolic dysregulation and tumor progression in a mouse model of triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2189.

The association between rapid growth and lipid profile: a systematic review and meta-analysis.

Metabolic disease prevalence has increased in many regions, and is closely associated with dyslipidemia. Rapid growth refers to a significant increase in growth velocity above the normal range, particularly in infants and children, and is highly prevalent in congenital deficiency infants. But the association between dyslipidemia and rapid growth remains controversial. We performed this meta-analysis to investigate the lipid profile in subjects with and without postnatal rapid growth, and to determine what are the confounding factors. Medline, EMBASE, China National Knowledge Infrastructure Chinese citation database and WANFANG database were searched (last search in May 2021). Publication bias was examined by constructing funnel plots, Egger's linear regression test and Begg's rank correlation test. The fixed effects model would be adopted if I2 is less than 25%, otherwise random effects model would be used. There were 11 articles involved with a total of 1148 participants (539 boys and 609 girls, mean age=7.4 years). Pooled analysis found that rapid growth was negatively associated with high-density lipoprotein cholesterol (HDL-C) (weighted mean difference=-0.068, 95%CI [-0.117, -0.020]), but not associated with triglycerides (TG), total cholesterol (TC), or low-density lipoprotein cholesterol (LDL-C). Stratified analysis suggested that increased TG were found in rapid growth subjects from developing countries. Higher TC was observed for rapid growth participants of follow-up age ≤8 years old, rapid growth duration ≤2 years, preterm, low birth weight, and from developing countries. But decreased TC was observed in small for gestational age (SGA) rapid growth subjects. Decreased LDL-C had been documented in rapid growth subjects of follow-up age >8 years old, from developed countries, and SGA. At last, rapid growth groups had lower HDL-C in infants of rapid growth duration >2 years and from developed countries. Rapid growth is associated with lipid profiles, particularly during early childhood, and this relationship is influenced by factors such as the duration of growth, the level of national development, and birth weight. These findings are significant for the development of strategies to prevent metabolic diseases.This review was registered in PROSPERO International Prospective Register of Systematic Reviews (www.crd.york.ac.uk/prospero/) with the registration number CRD42020154240.

Physiological and psychological determinants of long-term diet-induced type 2 diabetes (T2DM) remission: A narrative review.

Type 2 diabetes mellitus (T2DM) is a highly prevalent metabolic disease, causing a heavy burden on healthcare systems worldwide, with related complications and anti-diabetes drug prescriptions. Recently, it was demonstrated that T2DM can be put into remission via significant weight loss using low-carbohydrate diets (LCDs) and very low-energy diets (VLEDs) in individuals with overweight and obesity. Clinical trials demonstrated remission rates of 25-77%, and metabolic improvements such as improved blood lipid profile and blood pressure were observed. In contrast, clinical trials showed that remission rate declines with time, concurrent with weight gain, or diminished weight loss. This review aims to discuss existing literature regarding underlying determinants of long-term remission of T2DM including metabolic adaptations to weight loss (e.g., role of gastrointestinal hormones), type of dietary intervention (i.e., LCDs or VLEDs), maintaining beta (β)-cell function, early glycemic control, and psychosocial factors. This narrative review is significant because determining the factors that are associated with challenges in maintaining long-term remission may help in designing sustainable interventions for type 2 diabetes remission.

Hormonal Contraception and Risk of Cardiometabolic Disease in Women with HIV.

Objective: We sought to determine the association of hormonal contraception (HC) and cardiometabolic outcomes among women with human immunodeficiency virus (HIV). Methods: We included women with HIV aged 18-45 years in clinical care in the Southeastern United States between 1998 and 2018. Oral and injectable HC use was captured from medication records. Our outcomes included incident cardiovascular/thrombotic disease (CVD) (atherosclerosis, hypertension, cerebrovascular disease, thrombosis, and heart failure) and incident metabolic disorders (diabetes, dyslipidemia, obesity, and non-alcoholic steatohepatitis). We excluded women with prevalent conditions. We used multivariable marginal structural models to examine time-varying current and cumulative HC use and cardiometabolic outcomes in separate analyses, adjusting for age, race, smoking, time-varying comorbidities, CD4 cell count, HIV RNA, and antiretroviral use. Women with HC exposure were compared with women without HC exposure. Results: Among the 710 women included, 201 women (28%) used HC. CVD analyses included 603 women without prevalent CVD and 93 incident events; metabolic analyses included 365 women without prevalent metabolic disease and 150 incident events. Current and cumulative oral HC use was associated with increased odds of CVD, though this was not statistically significant (adjusted odds ratio [aOR] = 2.08, [95% confidence interval (CI): 0.80-5.43] and aOR = 1.24 [95% CI: 0.96-1.60] per year of use, respectively). Oral HC was not associated with risk of incident metabolic disorders. Depot medroxyprogesterone acetate (DMPA) was not associated with risk of incident CVD. Current and cumulative DMPA use was significantly associated with decreased odds of incident metabolic disorders (aOR = 0.48 [95% CI: 0.23, 1.00] and aOR = 0.65 [95% CI: 0.42-1.00] per year of use, respectively). Conclusion: Our results suggest that cardiovascular risk should be considered when selecting contraception for women with HIV.

Animal studies on glucagon-like peptide-1 receptor agonists and related polyagonists in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is a prevalent metabolic liver disease closely associated with the epidemics of obesity and type 2 diabetes mellitus (T2DM), but without licensed pharmacological treatment to date. As glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) are approved anti-diabetic and anti-obesity medications, they were also considered a potential therapeutic option for NAFLD. Preclinical studies suggest that GLP-1RAs have a beneficial effect on major NAFLD histological outcomes, i.e., hepatic steatosis and inflammation, through multiple intrahepatic mechanisms, including increased fatty acid β-oxidation, activation of autophagy, suppression of inflammation, and oxidative stress. Data on hepatic fibrosis are limited or inconclusive, although some studies reported improvement in indices of fibrosis or prevention of fibrosis initiation or reduction of collagen deposition. Whether the positive impact of GLP-1RAs on hepatic histology is indirect, i.e., through their action on extrahepatic tissues, or whether their action is direct, i.e., through activating GLP-1R on the hepatocytes, is still a controversial issue. Alongside GLP-1RAs, newly emerging peptide polyagonists (i.e., synthetic molecules that combine the amino acid sequences of more than one peptide, thus having the ability to bind more than one receptor) are now being investigated in NAFLD with high expectations. This review summarizes the existing knowledge derived from animal studies on the effects of GLP-1RAs and GLP-1RA related peptide polyagonists on NAFLD in an attempt to illuminate areas of uncertainty and provide the groundwork for future animal and clinical research in the field.

Insulin resistance and metabolic diseases - a review

Introduction: This review paper aims to discuss the effects of insulin resistance, and its association with various metabolic diseases. Insulin resistance (IR), characterized by diminished tissue responsiveness to physiological insulin levels, is a key component in various metabolic diseases, including type 2 diabetes, cardiovascular disorders (CVDs), obesity, and non-alcoholic fatty liver disease (NAFLD).
 State of knowledge The consequences of IR are profound; in type 2 diabetes, it hinders glucose utilization by muscle cells, leading to hyperglycemia, muscle damage, and loss of mass and strength. IR also plays a central role in NAFLD, promoting lipid accumulation, hepatic inflammation, fibrosis, and cell death.
 Materials and methods: A review of chosen literature in the PubMed and Google Scholar databases was conducted, using the following key words: „Insulin resistane”, „Insulin resistance in obesity”, „Obesity”, „Insulin resistance NAFLD”, „Diebetes”, „Insulin resistance CVD”
 Summary: The consequences of insulin resistance are far-reaching. In the context of type 2 diabetes, it impedes glucose utilization by muscle cells, resulting in hyperglycemia and subsequent muscle cell damage, contributing to loss of mass and strength. Insulin resistance is also a central player in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), fostering lipid accumulation, hepatic inflammation, and, ultimately, fibrosis and cell death.
 Conclusions: In conclusion, understanding insulin resistance is paramount in addressing the rising prevalence of metabolic diseases globally Controlling insulin resistance emerges as a crucial aspect of managing these metabolic disorders and their complications. Further research into the mechanisms of IR formation and effective intervention strategies is imperative for improving public health outcomes.

Scallop mantle-derived exosomes promote osteoblast formation and alleviate osteoporosis in mice

Osteoporosis, the most prevalent metabolic bone disease, has emerged as a serious public health concern. Safe and effective therapeutic interventions for osteoporosis are urgently needed. Here, we demonstrated that scallop mantle-derived exosomes (SMEs) promoted osteogenesis and prevented osteoporosis in ovariectomy-induced osteoporotic mice. Specifically, we successfully isolated SMEs with typical exosome morphology and desirable particle size. SMEs were found to contain abundant functional lipids, metabolites, and osteogenic-related proteins. Cell experiments revealed that SMEs could be internalized by osteoblastic MC3T3-E1 cells and promoted the proliferation, differentiation, and mineralization of MC3T3-E1 cells. In addition, SMEs survived the hostile gastrointestinal conditions and accumulated in the bone of mice after oral administration. Further mice investigations demonstrated that orally administered SMEs efficiently alleviated the bone loss, and improved the bone microstructure and biochemical properties in an ovariectomy-induced osteoporosis mouse model. Overall, these results reveal the osteogenesis effect of dietary SMEs, suggesting the potential of SMEs as an alternative or adjunct therapeutic agent in preventing or ameliorating osteoporosis.

Impact of Overseas Deployment on Fatty Liver and Metabolic Diseases Among Korean Soldiers

ABSTRACT Background The prevalence of metabolic diseases is increasing worldwide and is influenced by multiple environmental, psychological, and dietary factors. As overseas deployment (OD) of Korean soldiers brings about changes in these factors, this study aimed to explore the impact of OD on metabolic diseases. Materials and Methods We collected paired health checkup data of Korean soldiers between January 2020 and December 2022, before and after their deployment. We analyzed changes in lipid profile, fasting glucose, and liver function biomarkers during OD and compared the prevalence of metabolic diseases before and after the OD. Results A total of 2,953 soldiers were enrolled. During OD, body weight, body mass index, total cholesterol, low-density lipoprotein, and fasting glucose levels decreased significantly. Furthermore, the prevalence of obesity, impaired fasting glucose, and nonalcoholic fatty liver disease decreased significantly from 45.78% to 33.49%, P < .001; 38.60% to 34.41%, P < .001; and 24.89% to 18.88%, P < .001, respectively. In a subgroup analysis of participants with long-term deployment (duration >365 days), only the prevalence of obesity decreased significantly during deployment, whereas the prevalence of hypertension and dyslipidemia increased. Conclusions Metabolic biomarkers improved, and the prevalence of metabolic diseases decreased significantly during OD. However, personnel with long-term deployment did not experience significant improvements in these parameters. Further analysis is needed to identify the factors influencing these discrepancies.

Prevalence of Metabolic Disease among Adults in Indonesia: A Cross-Sectional Population-Based Survey

Introduction: Metabolic diseases were the leading cause of morbidity and mortality in the world. the World Health Organization, the effective delivery of public health messages has become increasingly complicated due to CKD as a complication of cardiovascular disease and diabetes. Studies have prevalence of metabolic disease among adults in Indonesia. These study aims were to determine the prevalence of kidney, cardiovascular, diabetes. Method: This study uses a cross-sectional study design used from Indonesia Family Life Survey Wave 5 (IFLS-5) organized by Rand Corporation conducted in 2014-2015. A statistical analysis is a descriptive observational study. The total number of respondents un this study was 27,718. Result: Respondents with adult criteria in Indonesia were 52.67% women aged 38.20(±13.64), 78.48% married, 32.94%elementary, and 59.89% urban residents. The prevalence of chronic kidney disease among adults in Indonesia was 1.43% (95% CI: 00.01 – 0.02). The prevalence of cardiovascular disease among adults in Indonesia was 1.64% (95% CI: 00.01 – 0.02). The prevalence of diabetes among adults in Indonesia was 2.33% (95% CI: 00.02 – 0.03). Conclusion: The prevalence of chronic kidney disease, cardiovascular disease, and diabetes in Indonesia is strongly by age and show a relationship between sufferers of these three diseases.

Curcumin Mitigates the High-Fat High-Sugar Diet-Induced Impairment of Spatial Memory, Hepatic Metabolism, and the Alteration of the Gut Microbiome in Alzheimer's Disease-Induced (3xTg-AD) Mice.

The escalating prevalence of metabolic diseases and an aging demographic has been correlated with a concerning rise in Alzheimer's disease (AD) incidence. This study aimed to access the protective effects of curcumin, a bioactive flavonoid from turmeric, on spatial memory, metabolic functions, and the regulation of the gut microbiome in AD-induced (3xTg-AD) mice fed with either a normal chow diet (NCD) or a high-fat high-sugar diet (HFHSD). Our findings revealed an augmented susceptibility of the HFHSD-fed 3xTg-AD mice for weight gain and memory impairment, while curcumin supplementation demonstrated a protective effect against these changes. This was evidenced by significantly reduced body weight gain and improved behavioral and cognitive function in the curcumin-treated group. These improvements were substantiated by diminished fatty acid synthesis, altered cholesterol metabolism, and suppressed adipogenesis-related pathways in the liver, along with modified synaptic plasticity-related pathways in the brain. Moreover, curcumin enriched beneficial gut microbiota, including Oscillospiraceae and Rikenellaceae at the family level, and Oscillibacter, Alistipes, Pseudoflavonifractor, Duncaniella, and Flintibacter at the genus level. The observed alteration in these gut microbiota profiles suggests a potential crosswalk in the liver and brain for regulating metabolic and cognitive functions, particularly in the context of obesity-associated cognitive disfunction, notably AD.

Recent progress in metabolic reprogramming in gestational diabetes mellitus: a review.

Gestational diabetes mellitus is a prevalent metabolic disease that can impact the normal course of pregnancy and delivery, leading to adverse outcomes for both mother and child. Its pathogenesis is complex and involves various factors, such as insulin resistance and β-cell dysfunction. Metabolic reprogramming, which involves mitochondrial oxidative phosphorylation and glycolysis, is crucial for maintaining human metabolic balance and is involved in the pathogenesis and progression of gestational diabetes mellitus. However, research on the link and metabolic pathways between metabolic reprogramming and gestational diabetes mellitus is limited. Therefore, we reviewed the relationship between metabolic reprogramming and gestational diabetes mellitus to provide new therapeutic strategies for maternal health during pregnancy and reduce the risk of developing gestational diabetes mellitus.

Potential therapeutic role of spermine via Rac1 in osteoporosis: Insights from zebrafish and mice.

Osteoporosis is a prevalent metabolic bone disease. While drug therapy is essential to prevent bone loss in osteoporotic patients, current treatments are limited by side effects and high costs, necessitating the development of more effective and safer targeted therapies. Utilizing a zebrafish ( Danio rerio) larval model of osteoporosis, we explored the influence of the metabolite spermine on bone homeostasis. Results showed that spermine exhibited dual activity in osteoporotic zebrafish larvae by increasing bone formation and decreasing bone resorption. Spermine not only demonstrated excellent biosafety but also mitigated prednisolone-induced embryonic neurotoxicity and cardiotoxicity. Notably, spermine showcased protective attributes in the nervous systems of both zebrafish embryos and larvae. At the molecular level, Rac1 was identified as playing a pivotal role in mediating the anti-osteoporotic effects of spermine, with P53 potentially acting downstream of Rac1. These findings were confirmed using mouse ( Mus musculus) models, in which spermine not only ameliorated osteoporosis but also promoted bone formation and mineralization under healthy conditions, suggesting strong potential as a bone-strengthening agent. This study underscores the beneficial role of spermine in osteoporotic bone homeostasis and skeletal system development, highlighting pivotal molecular mediators. Given their efficacy and safety, human endogenous metabolites like spermine are promising candidates for new anti-osteoporotic drug development and daily bone-fortifying agents.

Early Diagnosis of Risks and Management of Cardiometabolic Diseases: A Case Study

The case study presented underscores the importance of early identification of metabolic risks, effective management, and lifestyle modifications in preventing clinical complications associated with cardiometabolic diseases (CMDs). The individual in the study, a South Asian immigrant, experienced the development of essential hypertension in his mid-50s, leading to left ventricular hypertrophy (LVH) and mild diastolic dysfunction. However, through proactive measures such as early diagnosis of metabolic risks, robust management of cardiovascular disease (CVD), adherence to a heart-healthy diet, and lifestyle changes, he was able to avoid major clinical complications of diabetes and maintain overall well-being until the age of 87. The key takeaways from this case study align with broader public health initiatives aimed at addressing the global epidemic of metabolic diseases. The multifaceted and intricate nature of this problem requires a comprehensive approach that considers various factors contributing to the rising prevalence of these diseases. Primary prevention strategies, which focus on identifying and mitigating risk factors for CMDs before the onset of vascular disease, play a crucial role in curbing the epidemic. The success observed in this case study, highlights the potential impact of proactive management and lifestyle interventions, in preventing and mitigating the progression of cardiometabolic diseases. It emphasizes the need for increased awareness, early screening, and ongoing monitoring of individuals at risk. Additionally, promoting heart-healthy diets and encouraging lifestyle modifications, such as regular physical activity and stress reduction, are essential components of a holistic approach to cardiometabolic health. Despite the positive outcomes demonstrated in this case, the article acknowledges that the global response to preventing both communicable and non-communicable diseases has been tepid, with varying levels of enthusiasm for developing primary prevention strategies across different nations. Addressing this challenge requires coordinated efforts at the individual, community, and policy levels to promote a culture of preventive healthcare. In conclusion, the findings of this case study contribute to the growing body of evidence supporting the efficacy of early diagnosis of metabolic risks, effective management, and lifestyle modifications in preventing clinical complications associated with cardiometabolic diseases. The lessons learned from individual cases can inform broader public health initiatives and underscore the importance of a proactive and comprehensive approach to address the escalating prevalence of metabolic diseases globally

'Nine Steaming Nine Sun-drying' processing enhanced properties of Polygonatum kingianum against inflammation, oxidative stress and hyperglycemia.

Polygonatum kingianum Coll. & Hemsl (PK), a prominent medicine and food homology plant, has been consumed as a decoction from boiling water for thousands of years. 'Nine Steaming Nine Sun-drying' processing has been considered an effective method for enriching tonic properties, but studies investigating such impacts on PK and underlying mechanisms are extremely rare. We first demonstrated substantial improvements in the anti-oxidative, anti-inflammatory and anti-hyperglycemia effects of the Nine Steaming Nine Sun-drying processed PK water extracts compared with crude PK in cell models (i.e., HepG2 and Raw 264.7 cells). We then integrated foodomics and network pharmacology analysis to uncover the key compounds responsible for the improved benefits. A total of 551 metabolites of PK extracts were identified, including polyphenols, flavonoids, alkaloids, and organic acids. During processing, 204 metabolites were enhanced, and 32 metabolites were recognized as key constituents of processed PK responsible for the improved health-promoting activities, which may affect PI3K-Akt-, MAPK-, and HIF-1 pathways. We further confirmed the high affinity between identified key constituents of processed PK and their predicted acting targets using molecular docking. Our results provide novel insights into bioactive compounds of processed PK, elaborating the rationality of processing from the perspective of tonic effects. Consuming processed PK could be an efficacious strategy to combat the high prevalence of metabolic diseases that currently affect millions of people worldwide. © 2023 Society of Chemical Industry.