Huanglian-Jiedu decoction promotes adipose thermogenesis in obese mice by suppressing the expression of HDAC3.

ETHNOPHARMACOLOGICAL RELEVANCE: Huanglian Jiedu Decoction (HLJDD) is an ancient formula of traditional Chinese medicine that is commonly utilized in a range of disorders, and it has been shown to have pharmacological effects on glucose and lipid metabolism. However, the specific mechanism of HLJDD for the treatment of obesity and related metabolic disorders remains to be further investigated. AIM OF THE STUDY: It has been thought that encouraging adipose thermogenesis to raise the body's energy expenditure is a useful tactic for improving metabolic abnormalities and losing weight. In this study, we investigated the ability and underlying mechanisms of HLJDD to regulate fat cell thermogenesis to improve energy expenditure in obesity. METHODS: The obese mouse model was established on a high-fat diet for 12 weeks. All mice were divided into NC, HFD, HFD with HLJDD of a low dose (2.25 g/kg/d), and HFD with HLJDD of a high dose (4.5 g/kg/d) groups and kept for 4 weeks. In vitro experiments were conducted to evaluate the effects of 5% and 10% HLJDD-containing serum on differentiated 3T3-L1 cells and HDAC3-knocking-down 3T3-L1 cells. RESULTS: The results showed that HLJDD treatment significantly improved glucose and insulin tolerance and decreased the adipocyte radius of WATs, as well as increased energy consumption in obese mice. Besides, HLJDD treatment dramatically increased the levels of thermogenic genes UCP-1 and PGC-1α while suppressing HDAC3 levels in WATs and 3T3-L1 adipocytes. Importantly, the effects of HLJDD on PGC-1α and UCP-1 were blocked in HDAC3 knockdown adipocytes. CONCLUSIONS: Therefore, these results suggest that HLJDD enhanced adipose thermogenesis and improved energy expenditure by inhibiting HDAC3, thereby increasing UCP-1 and PGC-1α expression. These findings amplified the mechanisms of HLJDD and its potential to treat obesity and related metabolic disorders.

Emerging role of PES1 in disease: A promising therapeutic target?

Pescadillo ribosomal biogenesis factor 1 (PES1), a nucleolar protein initially identified in zebrafish, plays an important role in embryonic development and ribosomal biogenesis. Notably, PES1 has been found to be overexpressed in a number of cancer types, where it contributes to tumorigenesis and cancer progression by promoting cell proliferation, suppressing cellular senescence, modulating the tumor microenvironment (TME) and promoting drug resistance in cancer cells. Moreover, recent emerging evidence suggests that PES1 expression is significantly elevated in the livers of Type 2 diabetes mellitus (T2DM) and obese patients, indicating its involvement in the pathogenesis of metabolic diseases through lipid metabolism regulation. In this review, we present the structural characteristics and biological functions of PES1, as well as complexes in which PES1 participates. Furthermore, we comprehensively summarize the multifaceted role of PES1 in various diseases and the latest insights into its underlying molecular mechanisms. Finally, we discuss the potential clinical translational perspectives of targeting PES1, highlighting its promising as a therapeutic intervention and treatment target.

Roles of low muscle strength and sarcopenic obesity on incident symptomatic knee osteoarthritis: A longitudinal cohort study.

OBJECTIVES: Sarcopenia is prevalent in middle to old age. We aimed to investigate the association between muscle strength and the incident knee osteoarthritis (OA). METHODS: 12,043 participants were collected from the China Health and Retirement Longitudinal Study. The effects of sarcopenic obesity (defined by obesity in combination with possible sarcopenia) on knee OA onset were calculated using Poisson regression models. Mediation analysis was fit to estimate mediating proportion of muscle strength on the association between obesity and incident knee OA. RESULTS: The study all enrolled 12,043 participants with 2,008 progressed to knee OA. Poisson analyses demonstrated causal association of general obesity (RR:1.23, 95% CI: 1.08 to 1.39) and abdominal obesity (RR:1.23, 95% CI: 1.11 to 1.35) with knee OA onset. For the risk of incident knee OA, participants with the highest level of normalized grip strength had a decreased risk of incident knee OA by 0.33 (RR:0.67, 95% CI: 0.60 to 0.75) times compared to the control group, and chair-rising time was associated with increased risk of incident knee OA by 0.65 (RR:1.65, 95% CI: 1.17 to 2.33) times. Sensitivity analysis identified similar results. Participants with sarcopenic obesity were about 2 times risk of incident knee OA than reference group. Normalized grip strength and chair-rising time mediated the association between obesity and incidence of knee OA. CONCLUSIONS: Sarcopenic obesity is correlated with an increased risk of knee OA. Muscle strength recovery may alleviate the risk of incident knee OA in middle to old age with obesity.

Targeting osteoblastic 11ß-HSD1 to combat high-fat diet-induced bone loss and obesity.

Excessive glucocorticoid (GC) action is linked to various metabolic disorders. Recent findings suggest that disrupting skeletal GC signaling prevents bone loss and alleviates metabolic disorders in high-fat diet (HFD)-fed obese mice, underpinning the neglected contribution of skeletal GC action to obesity and related bone loss. Here, we show that the elevated expression of 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1), the enzyme driving local GC activation, and GC signaling in osteoblasts, are associated with bone loss and obesity in HFD-fed male mice. Osteoblast-specific 11ß-HSD1 knockout male mice exhibit resistance to HFD-induced bone loss and metabolic disorders. Mechanistically, elevated 11ß-HSD1 restrains glucose uptake and osteogenic activity in osteoblast. Pharmacologically inhibiting osteoblastic 11ß-HSD1 by using bone-targeted 11ß-HSD1 inhibitor markedly promotes bone formation, ameliorates glucose handling and mitigated obesity in HFD-fed male mice. Taken together, our study demonstrates that osteoblastic 11ß-HSD1 directly contributes to HFD-induced bone loss, glucose handling impairment and obesity.

Structure-function analysis of time-resolved immunological phases in metabolic dysfunction-associated fatty liver disease (MASH) comparing the NIF mouse model to human MASH.

Metabolic dysfunction-associated steatohepatitis (MASH) is a common but frequently unrecognized complication of obesity and type 2 diabetes. The association between these conditions is multifaceted and involves complex interactions between metabolic, inflammatory, and genetic factors. Here we assess the underlying structural and molecular processes focusing on the immunological phase of MASH in the nonobese inflammation and fibrosis (NIF) mouse model and compare it to the human disease as well as other murine models. Histopathology together with synchrotron-radiation-based x-ray micro-computed tomography (SRµCT) was used to investigate structural changes within the hepatic sinusoids network in the NIF mouse in comparison to patients with different severities of MASH. A time-course, bulk RNA-sequencing analysis of liver tissue from NIF mice was performed to identify the dynamics of key processes associated with the pathogenesis. Transcriptomics profiling of the NIF mouse revealed a gradual transition from an initially reactive inflammatory response to a regenerative, pro-fibrotic inflammatory response suggesting new avenues for treatment strategies that focus on immunological targets. Despite the lack of metabolic stress induced liver phenotype, a large similarity between the NIF mouse and the immunological phase of human MASH was detected. The translational value was further supported by the comparative analyses with MASH patients and additional animal models. Finally, the impact of diets known to induce metabolic stress, was explored in the NIF mouse. An obesogenic diet was found to induce key physiological, metabolic, and histologic changes akin to those observed in human MASH.

Association between bone microarchitecture and sarcopenia in postmenopausal women with type 2 diabetes.

Bone microarchitecture, as assessed using high-resolution peripheral quantitative computed tomography, is adversely affected in postmenopausal women with type 2 diabetes mellitus having sarcopenia/sarcopenic obesity while areal bone mineral density does not differ between those with and without sarcopenia. PURPOSE: Type 2 diabetes (T2D) increases the risk of sarcopenia, which independently contributes to bone fragility. We aimed to explore the association between sarcopenia/sarcopenic obesity and bone quality using second-generation high-resolution peripheral quantitative computed tomography (HR-pQCT) in T2D. METHODS: We analyzed the baseline participant characteristics of an ongoing randomized clinical pilot trial (CTRI/2022/02/039978). Postmenopausal women (≥ 50 years) with T2D and high risk of fragility fractures were included. Areal BMD (aBMD), trabecular bone score (TBS), and body composition were measured using DXA. Bone microarchitecture was assessed at distal radius/distal tibia using HR-pQCT. Muscle strength was estimated using dominant handgrip strength (HGS). Sarcopenia was defined as low HGS (< 18.0 kg) and low appendicular skeletal muscle index (ASMI) (< 4.61 kg/m2). Probable sarcopenia was defined as low HGS with normal ASMI. Sarcopenic obesity was classified as co-existence of sarcopenia and obesity (BMI ≥ 25.0 kg/m2). RESULTS: We recruited 129 postmenopausal women (mean age 64.2 ± 6.7 years). Participants were categorized into four mutually exclusive groups: group A (normal HGS and ASMI, n = 17), group B (probable sarcopenia, n = 77), group C (non-obese sarcopenia, n = 18), and group D (obese sarcopenia, n = 18). The four groups did not differ significantly with regard to baseline characteristics, fracture prevalence, HbA1c, aBMD, and TBS. However, HR-pQCT-derived volumetric BMD and cortical/trabecular microarchitecture were significantly poorer in group C/group D than in group A/group B. CONCLUSIONS: Bone quality rather than bone density (quantity) is adversely affected in T2D postmenopausal women with sarcopenia/sarcopenic obesity, which could increase the fracture risk in this patient sub-population.

Normal caloric intake with high-fat diet induces metabolic dysfunction-associated steatotic liver disease and dyslipidemia without obesity in rats.

Excessive caloric intake and obesity due to high-fat (HFD) and high-disaccharide (HDD) diets have been recognized as major contributing factors to dyslipidemia and metabolic dysfunction-associated steatotic liver disease (MASLD). However, the effect of HFD and HDD without excessive caloric intake is obscure. The aim of the study was to evaluate the effect of physiological caloric intake delivered through HFD and HDD on liver and lipid profiles. The study was performed on 6-week-old male and female (50/50%) Sprague Dawley rats, receiving either a standard (controls, n = 16), HFD (n = 14) or HDD (n = 14) chow. All groups received the same, standard daily calorie rations, titrated weekly to the age of growing rats, for 12 weeks. A panel of metabolic in vivo measurement were performed, followed by histological, biochemical and molecular biology assays on tissues harvested from sacrificed rats. There was no significant difference between the groups in body weight. In contrast to controls, HFD and HDD groups showed metabolic dysfunction-associated steatohepatitis (MASH) characterized by liver steatosis, inflammation, ballooning of hepatocytes and fibrosis. These changes were more pronounced in the HFD than in the HDD group. The HFD group showed significantly higher serum LDL than controls or HDD rats. Furthermore, the HFD group had higher liver protein levels of low-density lipoprotein receptor (LDLR) but lower plasma levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) than the controls or HDD group. There were no differences between sexes in evaluated parameters. The excessive caloric intake and obesity are not prerequisites for the development of MASH and dyslipidemia in rats. The liver changes induced by the HFD and HDD diets exhibit differences in severity, as well as in the expression patterns of LDLR and PCSK9. Notably, these effects are independent of the sex of the rats.

Sleeve gastrectomy ameliorates renal injury in obesity-combined hyperuricemic nephropathy mice by modulating the AMPK/Nrf2/ABCG2 pathway.

Hyperuricemic nephropathy (HN) is renal injury caused by hyperuricemia (HUA). While sleeve gastrectomy (SG) has shown promise in improving renal injury in patients with obesity-related HN, the mechanisms are not fully understood. This study induced an obesity-combined HN model in male ob/ob mice and measured serum uric acid (SUA), creatinine, and other biochemical indicators 6 weeks post-surgery. Renal histological changes were evaluated through staining techniques, and the study also assessed renal adenosine monophosphate-activated protein kinase (AMPK) and nuclear factor erythroid 2-related factor 2 (Nrf2) phosphorylation levels and urate transporter ABCG2 expression. In vitro experiments involved Nrf2 knockdown in AMPK-activated HK-2 cells and ChIP to confirm Nrf2 binding to the ABCG2 promoter. Results showed that SG reduced SUA levels, serum creatinine, and blood urea nitrogen, increased p-AMPK, p-Nrf2 protein, and ABCG2 expression, and alleviated renal fibrosis and inflammation. In vitro, Nrf2 knockdown down-regulated ABCG2 expression, and ChIP confirmed Nrf2's role in ABCG2 transcription. The study suggests that SG may improve renal injury in HN mice by modulating the AMPK/Nrf2 pathway and upregulating ABCG2 transcription.

Curcumin extract improves beta cell functions in obese patients with type 2 diabetes: a randomized controlled trial.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a chronic condition characterized by insulin resistance and impaired insulin production, leading to elevated blood glucose levels. Curcumin, a polyphenolic compound from Curcuma longa, has shown potential in improving insulin sensitivity and reducing blood glucose levels, which may help mitigate type 2 diabetes progression. OBJECTIVE: To assess the efficacy of improving type 2 diabetes (T2DM). STUDY DESIGN: This randomized, double-blind, placebo-controlled trial included subjects (n = 272) with criteria for type 2 diabetes. METHODS: All subjects were randomly assigned to receive curcumin (1500 mg/day) or placebo with blind labels for 12 months. To assess the improvement of T2DM after curcumin treatments body weight and body mass index, fasting plasma glucose, glycosylated hemoglobin A1c, ß-cell function (homeostasis model assessment [HOMA-ß]), insulin resistance (HOMA-IR), insulin, adiponectin, and leptin were monitored at the baseline and at 3-, 6-, 9-, and 12-month visits during the course of intervention. RESULTS: After 12 months of treatment, the curcumin-treated group showed a significant decrease in fasting blood glucose (115.49 vs.130.71; P < 0.05), HbA1c (6.12 vs. 6.47; P < 0.05). In addition, the curcumin-treated group showed a better overall function of ß-cells, with higher HOMA-ß (136.20 vs. 105.19; P < 0.01) The curcumin-treated group showed a lower level of HOMA-IR (4.86 vs. 6.04; P < 0.001) and higher adiponectin (14.51 vs. 10.36; P < 0.001) when compared to the placebo group. The curcumin-treated group also showed a lower level of leptin (9.42 vs. 20.66; P < 0.001). Additionally, body mass index was lowered (25.9 4 vs.29.34), with a P value of 0.001. CONCLUSIONS: A 12-month curcumin intervention in type 2 diabetes patients shows a significant glucose-lowering effect. Curcumin treatment appeared to improve the overall function of ß-cells and reduce both insulin resistance and body weight, with very minor adverse effects. Curcumin intervention in obese patients with type 2 diabetes may be beneficial. TRIAL REGISTRATION: Thai clinical trials regentrify no.20140303003.

Differences in sarcopenia indices in elderly Japanese women and their relationships with obesity classified according to waist circumference, BMI, and body fat percentage.

BACKGROUND: Sarcopenic obesity (SO) is defined as a decrease in lean body mass and an increase in body fat mass (BFM) due to aging. Detecting SO in elderly women is important from the perspective of extending healthy life expectancy. While various indices of SO are currently used, there is no global consensus regarding diagnostic criteria for SO. This study aimed to examine the relationship between obesity indices (waist circumference (WC), body mass index (BMI), and body fat percentage (BFP)) and sarcopenia indices (total body muscle mass (TBM), appendicular lean mass (ALM), skeletal mass index (SMI)), and physical function (gait speed (GS), handgrip strength (HGS)). METHODS: Subjects were 170 community-dwelling healthy elderly women aged 65-79 years (mean: 72.7 ± 5.78 years) who underwent measurements for WC, BMI, and BFP. A WC of ≥ 90cm was defined as the obese group, BMI was determined as weight (kg) divided by height squared (m2) and a cutoff of ≥ 25 kg/m2 was used to define the obesity group. BFM was measured using the bioelectrical impedance analysis (BIA) method and BFP was calculated from body weight and a cutoff of ≥ 30% was used to define the obesity group. TBM and ALM (kg) were measured using the BIA method, ALM (kg) was corrected for height (m2) to obtain SMI (kg/m2). Physical function was assessed by GS and HGS, which were measured by the 5-m walk test and a digital grip strength meter, respectively. RESULTS: When obesity was assessed using BMI, WC and BFP, obese individuals had higher TBM, ALM and SMI, and lower GS among the sarcopenia indicators. HGS did not differ significantly between the non-obese and obese groups. CONCLUSION: Our findings suggest HGS is thought to reflect muscle strength without being affected by obesity indices, suggesting that it may be useful in detecting possible sarcopenia in obese individuals.

Trends and determinants of clustering for non-communicable disease risk factors in women of reproductive age in Nepal.

BACKGROUND: Understanding the clustering of two or more risk factors of non-communicable disease, such as smoking, overweight/obesity, and hypertension, among women of reproductive age could facilitate the design and implementation of strategies for prevention and control measures. This study examined the factors associated with smoking, overweight/obesity, and hypertension among Nepalese women of reproductive age (15-49 years). METHODS: This study used the Nepal Demographic and Health Surveys (NDHS) 2016 (6,079 women for smoking and overweight/obesity, 6076 for hypertension) and 2022 (6,957 women for overweight/obesity and smoking status and 3,749 women for hypertension) for comparison of trends of NCD risk factors among women aged 15-49 years. Additionally, for each participant, risk factors score (range of 0 to 3) was created by summing individual risk factors. We assessed the determinants of risk factor clustering using multivariable Poisson regression models with robust sandwich variance estimator to calculate adjusted prevalence ratios using NDHS 2022. RESULTS: The national prevalence of overweight/obesity increased from 22.2% in 2016 to 29.2% in 2022 among women of reproductive age. In 2022, the prevalence for smoking, overweight/obesity, and hypertension were 3.8%, 29.2%, and 9.6%, respectively. More than one in four women (28.7%) had one NCD risk factor, while 6.5% had two such risk factors. Higher aged women (40-49 years) were more likely to have multiple NCD risk factors than those aged 15-29 years (APR: 3.19; 95% CI: 2.68-3.80). Those in the richest wealth quintile (APR: 1.52; 95% CI: 1.24-1.85), as well as married (APR: 3.02; 95% CI: 2.43-3.76) and widowed/divorced (APR: 2.85; 95% CI: 2.14-3.80) were more likely to have multiple NCD risk factors. Women from Koshi province (APR: 1.74; 95% CI: 1.41-2.15) had more NCD risk factors than those from the Sudurpaschim province. Working women also had a higher prevalence of NCD risk factors compared to non-working women (APR: 1.23; 95% CI: 1.06-1.43). Additionally, Hill Janajatis (APR: 1.44; 95% CI: 1.21-1.72) and Dalits (APR: 1.42; 95% CI: 1.15-1.75) women were more likely to have NCD risk factors compared to women of Brahmin hill origin. CONCLUSIONS: Clustering of two or more NCD risk factors was higher among women aged ≥30 years, those who are currently married or widowed/divorced/separated, working women, and individuals from the wealthiest socioeconomic groups. A higher burden of risk factors underscores the importance of targeted public health interventions, particularly among women from advantaged socio-economic groups, those of affluent regions, and in the workplace.

Diosgenin Alleviates Obesity-Induced Insulin Resistance by Modulating PI3K/Akt Signaling Pathway in Mice Fed a High-Fat Diet.

Obesity is a global medical issue that can be effectively treated by relieving adipose inflammation and subsequent insulin resistance. Diosgenin (DIOS) has various effects as a steroidal saponin in inflammatory disorders. This study explored the effects and mechanism of DIOS on adipose inflammation and insulin sensitivity, both in silico and in vivo. The high-fat diet-induced obesity model in C57BL/6 mice was divided into five groups: normal chow (NC), high-fat diet (HFD), HFD with atorvastatin 10 mg/kg (AT), HFD with DIOS 100 mg/kg (DIOS 100), and HFD with DIOS 200 mg/kg (DIOS 200). Each group underwent an oral intervention for seven weeks. DIOS significantly suppressed weight gain in the body, liver, and epididymal fat pads. Additionally, it significantly improved fasting glucose and insulin levels, homeostatic model assessment of insulin resistance (HOMA-IR), and oral glucose tolerance test results, and reduced the proportion of total and M1 adipose tissue macrophages. Significant changes were shown in mRNA expression of janus kinase 2 (JAK2), insulin receptor (INRS), insulin receptor substrate 1 (IRS-1), phosphatidylinositol 3-kinase (PI3K), and protein kinase B (Akt), all of which exhibited high binding affinity in the in silico. Safety indices, including aspartate aminotransferase (AST), alanine transaminase (ALT), and creatinine level indicated the preventive effects of DIOS. In conclusion, DIOS improves insulin resistance and obesity-associated inflammation via the PI3K/Akt signaling pathway.

Effect of body mass index on ovarian reserve and ART outcomes in infertile women: a large retrospective study.

BACKGROUND: Obesity poses a significant global health challenge, with profound implications for women's reproductive health. The relationship between ovarian reserve and body mass index (BMI) remains a subject of debate. While obesity is generally associated with poorer outcomes in assisted reproductive technology (ART), the evidence remains inconclusive. This study aimed to investigate the effect of pre-pregnancy BMI on ovarian reserve and ART outcomes in infertile patients. METHODS: We conducted a retrospective cohort study involving women who underwent in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) procedures at Tongji Hospital between 2016 and 2023. The study included 30,746 initial fresh cycles and 5,721 singleton deliveries. Patients were stratified by age and further categorized into four BMI groups: lean (< 18.5 kg/m²), normal weight (18.5-24.9 kg/m²), overweight (25.0-29.9 kg/m²), and obese (≥ 30.0 kg/m²). The primary endpoints of the study were pregnancy and perinatal outcomes. To explore the association between BMI and these outcomes, we adjusted for relevant confounding factors and utilized multivariate linear regression models, complemented by multifactorial logistic regression analyses. RESULTS: Anti-Müllerian hormone (AMH) levels were significantly lower in the overweight and obese groups compared to the normal weight group. After adjusting for age, a negative correlation was found between AMH and BMI in the age subgroups of 20-30 and 30-35 years. Among women aged 20-35 years, those in the overweight and obese groups had significantly fewer retrieved oocytes, mature oocytes, and two-pronuclear (2PN) embryos than their normal weight counterparts. Despite these differences, pregnancy outcomes in the overweight and obese groups were comparable to those in the normal weight group across all age categories. Additionally, obesity was linked to an increased risk of gestational diabetes mellitus, hypertensive disorders of pregnancy, and macrosomia. CONCLUSIONS: An age-related decrease in AMH levels was evident with increasing BMI. Although being overweight or obese is associated with poorer embryo and perinatal outcomes, it does not seem to have a substantial impact on fertility.

Longitudinal associations between microRNAs and weight in the diabetes prevention program.

Objective: Circulating microRNAs show cross-sectional associations with overweight and obesity. Few studies provided data to differentiate between a snapshot perspective on these associations versus how microRNAs characterize prodromal risk from disease pathology and complications. This study assessed longitudinal relationships between circulating microRNAs and weight at multiple time-points in the Diabetes Prevention Program trial. Research design and methods: A subset of participants (n=150) from the Diabetes Prevention Program were included. MicroRNAs were measured from banked plasma using a Fireplex Assay. We used generalized linear mixed models to evaluate relationships between microRNAs and changes in weight at baseline, year-1, and year-2. Logistic regression was used to evaluate whether microRNAs at baseline were associated with weight change after 2 years. Results: In fully adjusted models that included relevant covariates, seven miRs (i.e., miR-126, miR-15a, miR-192, miR-23a, and miR-27a) were statistically associated with weight over 2 years. MiR-197 and miR-320a remained significant after adjustment for multiple comparisons. Baseline levels of let-7f, miR-17, and miR-320c were significantly associated with 3% weight loss after 2 years in fully adjusted models. Discussion: This study provided evidence for longitudinal relationships between circulating microRNAs and weight. Because microRNAs characterize the combined effects of genetic determinants and responses to behavioral determinants, they may provide insights about the etiology of overweight and obesity in the context or risk for common, complex diseases. Additional studies are needed to validate the potential genes and biological pathways that might be targeted by these microRNA biomarkers and have mechanistic implications for weight loss and disease prevention.

The effect of diets with different inflammatory scores on inflammation and sleep in obese subjects: a randomized controlled trial.

OBJECTIVE: The aim of this study was to investigate the effect of different dietary inflammatory index diets on inflammatory markers, anthropometric measurements, and sleep quality in obese subjects. METHODS: This study was conducted in a public hospital in Turkey between November 2021 and May 2022. Participants with pro-inflammatory dietary habits were included in the study. Randomly divided into two groups of 33 participants, they were subjected to an anti-inflammatory diet or a control diet for 8 weeks. The study evaluated the anthropometric parameters, inflammatory biomarkers, and sleep quality indices of the diet groups. RESULTS: Significant reductions in body mass index were observed in both groups, more marked in the anti-inflammatory diet cohort. C-reactive protein levels, indicative of inflammation, also decreased substantially in both groups, with a more marked reduction in the anti-inflammatory diet cohort. Despite the improvement in sleep quality in both groups, the variation was not statistically significant. CONCLUSION: This study demonstrates the importance of anti-inflammatory diets in nutritional strategies for obesity by reducing body mass index and inflammation.

GLP-1 programs the neurovascular landscape.

Readily available nutrient-rich foods exploit our inherent drive to overconsume, creating an environment of overnutrition. This transformative setting has led to persistent health issues, such as obesity and metabolic syndrome. The development of glucagon-like peptide-1 receptor (GLP-1R) agonists reveals our ability to pharmacologically manage weight and address metabolic conditions. Obesity is directly linked to chronic low-grade inflammation, connecting our metabolic environment to neurodegenerative diseases. GLP-1R agonism in curbing obesity, achieved by impacting appetite and addressing associated metabolic defects, is revealing additional benefits extending beyond weight loss. Whether GLP-1R agonism directly impacts brain health or does so indirectly through improved metabolic health remains to be elucidated. In exploring the intricate connection between obesity and neurological conditions, recent literature suggests that GLP-1R agonism may have the capacity to shape the neurovascular landscape. Thus, GLP-1R agonism emerges as a promising strategy for addressing the complex interplay between metabolic health and cognitive well-being.

Potentially Modifiable Dementia Risk Factors in Canada: An Analysis of Canadian Longitudinal Study on Aging with a Multi-Country Comparison.

BACKGROUND: It has been suggested that up to 40% of dementia cases worldwide are associated with modifiable risk factors; however, these estimates are not known in Canada. Furthermore, sleep disturbances, an emerging factor, has not been incorporated into the life-course model of dementia prevention. OBJECTIVE: To estimate the population impact of 12 modifiable risk factors in Canadian adults including sleep disturbances, by sex and age groups, and to compare with other countries. DESIGN: Cross-sectional analysis of Canadian Longitudinal Study on Aging baseline data. SETTING: Community. PARTICIPANTS: 30,097 adults aged 45 years and older. MEASUREMMENTS: Prevalence and Population Attributable Fractions (PAFs) associated with less education, hearing loss, traumatic brain injury, hypertension, excessive alcohol, obesity, smoking, depression, social isolation, physical inactivity, diabetes, and sleep disturbances. RESULTS: The risk factors with the largest PAF were later life physical inactivity (10.2%; 95% CI, 6.8% to 13%), midlife hearing loss (6.5%; 3.7% to 9.3%), midlife obesity (6.4%; 4.1% to 7.7%), and midlife hypertension (6.2%; 2.7% to 9.3%). The PAF of later life sleep disturbances was 3.0% (95% CI, 1.8% to 3.8%). The 12 risk factors accounted for 51.9% (32.2% to 68.0%) of dementia among men and 52.4% (32.5% to 68.7%) among women. Overall, the combined PAF of all risk factors was 49.2% (31.1% to 64.9%), and it increased with age. CONCLUSION: Nearly up to 50% of dementia cases in Canada are attributable to 12 modifiable risk factors across the lifespan. Canadian risk reduction strategies should prioritize targeting physical inactivity, hearing loss, obesity, and hypertension.

Adipose tissue-derived extracellular vesicles aggravate temporomandibular joint osteoarthritis associated with obesity.

INTRODUCTION: Temporomandibular joint osteoarthritis (TMJ OA) is a major disease that affects maxillofacial health and is characterised by cartilage degeneration and subchondral bone remodelling. Obesity is associated with the exacerbation of pathological manifestations of TMJ OA. However, the underlying mechanism between adipose tissue and the TMJ axis remains limited. OBJECTIVES: To evaluate the effects of obesity and the adipose tissue on the development of TMJ OA. METHODS: The obesity-related metabolic changes in TMJ OA patients were detected by physical signs and plasma metabolites. The effects of adipose tissue-derived EVs (Ad-EVs) on TMJ OA was investigated through histological and cytological experiments as well as gene editing technology. Alterations of Ad-EVs in obese state were identified by microRNA-seq analysis and the mechanism by which EVs affect TMJ OA was explored in vitro and in vivo. RESULTS: Obesity and the related metabolic changes were important influencing factors for TMJ OA. Ad-EVs from obese mice induced marked chondrocyte apoptosis, cartilage matrix degradation and subchondral bone remodelling, which exacerbated the development of TMJ OA. Depletion of Ad-EVs secretion by knocking out the geranylgeranyl diphosphate synthase (Ggpps) gene in adipose tissue significantly inhibited the obesity-induced aggravation of TMJ OA. MiR-3074-5p played an important role in this process . CONCLUSIONS: Our work unveils an unknown link between obese adipose tissue and TMJ OA. Targeting the Ad-EVs and the miR-3074-5p may represent a promising therapeutic strategy for obesity-related TMJ OA. KEY POINTS: High-fat-diet-induced obesity aggravate the progression of TMJ OA in mice. Obese adipose tissue participates in cartilage damage through the altered miRNA in extracellular vesicles. Inhibition of miR-3074-5p/SMAD4 pathway in chondrocyte alleviated the effect of HFD-EVs on TMJ OA.

Impact of metabolic syndrome components on clinical outcomes in hypertriglyceridemia-induced acute pancreatitis.

BACKGROUND: The incidence of hypertriglyceridemia (HTG)-induced acute pancreatitis (AP) is steadily increasing in China, becoming the second leading cause of AP. Clinical complications and outcomes associated with HTG-AP are generally more severe than those seen in AP caused by other etiologies. HTG-AP is closely linked to metabolic dysfunction and frequently coexists with metabolic syndrome or its components. However, the impact of metabolic syndrome components on HTG-AP clinical outcomes remains unclear. AIM: To investigate the impact of metabolic syndrome component burden on clinical outcomes in HTG-AP. METHODS: In this retrospective study of 255 patients diagnosed with HTG-AP at the First Affiliated Hospital of Guangxi Medical University, we collected data on patient demographics, clinical scores, complications, and clinical outcomes. Subsequently, we analyzed the influence of the presence and number of individual metabolic syndrome components, including obesity, hyperglycemia, hypertension, and low high-density lipoprotein cholesterol (HDL-C), on the aforementioned parameters in HTG-AP patients. RESULTS: This study found that metabolic syndrome components were associated with an increased risk of various complications in HTG-AP, with low HDL-C being the most significant risk factor for clinical outcomes. The risk of complications increased with the number of metabolic syndrome components. Adjusted for age and sex, patients with high-component metabolic syndrome had significantly higher risks of renal failure [odds ratio (OR) = 3.02, 95%CI: 1.12-8.11)], SAP (OR = 5.05, 95%CI: 2.04-12.49), and intensive care unit admission (OR = 6.41, 95%CI: 2.42-16.97) compared to those without metabolic syndrome. CONCLUSION: The coexistence of multiple metabolic syndrome components can synergistically worsen the clinical course of HTG-AP, making it crucial to monitor these components for effective disease management.

Directly targeting PRDM16 in thermogenic adipose tissue to treat obesity and its related metabolic diseases.

Obesity is increasing globally and is closely associated with a range of metabolic disorders, including metabolic associated fatty liver disease, diabetes, and cardiovascular diseases. An effective strategy to combat obesity involves stimulating brown and beige adipocyte thermogenesis, which significantly enhances energy expenditure. Recent research has underscored the vital role of PRDM16 in the development and functionality of thermogenic adipocytes. Consequently, PRDM16 has been identified as a potential therapeutic target for obesity and its related metabolic disorders. This review comprehensively examines various studies that focus on combating obesity by directly targeting PRDM16 in adipose tissue.