The metabolic effects of habitual leg shaking: A randomized crossover trial.

Aims: The adverse effects of sedentary behavior on obesity and chronic diseases are well established. However, the prevalence of sedentary behavior has increased, with only a minority of individuals meeting the recommended physical activity guidelines. This study aimed to investigate whether habitual leg shaking, a behavior traditionally considered unfavorable, could serve as an effective strategy to improve energy metabolism.

Effect of 5:2 Regimens: Energy-Restricted Diet or Low-Volume High-Intensity Interval Training Combined With Resistance Exercise on Glycemic Control and Cardiometabolic Health in Adults With Overweight/Obesity and Type 2 Diabetes: A Three-Arm Randomized Controlled Trial.

Objective: We aimed to examine the effects of a 5:2 diet (2 days per week of energy restriction by formula diet) or an exercise (2 days per week of high-intensity interval training and resistance training) intervention compared with routine lifestyle education (control) on glycemic control and cardiometabolic health among adults with overweight/obesity and type 2 diabetes.

Research Design And Methods: This two-center, open-label, three-arm, parallel-group, randomized controlled trial recruited 326 participants with overweight/obesity and type 2 diabetes and randomized them into 12 weeks of diet intervention (n = 109), exercise intervention (n = 108), or lifestyle education (control) (n = 109). The primary outcome was the change of glycemic control measured as glycated hemoglobin (HbA1c) between the diet or exercise intervention groups and the control group after the 12-week intervention.

NPC1 is required for postnatal islet β cell differentiation by maintaining mitochondria turnover.

NPC1 is a protein localized on the lysosome membrane regulating intracellular cholesterol transportation and maintaining normal lysosome function. GWAS studies have found that variants in T2D was a pancreatic islet expression quantitative trait locus, suggesting a potential role of NPC1 in T2D islet pathophysiology. Two-week-old mice and wild type littermates were employed to examine pancreatic β cell morphology and functional changes induced by loss of .

A genome-wide association study of neutrophil count in individuals associated to an African continental ancestry group facilitates studies of malaria pathogenesis.

Background: 'Benign ethnic neutropenia' (BEN) is a heritable condition characterized by lower neutrophil counts, predominantly observed in individuals of African ancestry, and the genetic basis of BEN remains a subject of extensive research. In this study, we aimed to dissect the genetic architecture underlying neutrophil count variation through a linear-mixed model genome-wide association study (GWAS) in a population of African ancestry (N = 5976). Malaria caused by P.

Body size, insulin sensitivity, metabolic health and risk of cardiovascular disease in Chinese adults: Insights from the China Cardiometabolic Disease and Cancer Cohort (4C) study.

Aims: To assess the excess risk of cardiovascular disease (CVD) associated with different criteria for metabolic health, and the interplay of body size, insulin sensitivity and metabolic health with CVD risk.

Materials And Methods: We conducted a prospective study involving 115 638 participants from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. Metabolic health was defined using three different definitions: (1) insulin sensitivity defined by homeostatic model assessment of insulin resistance index; (2) absence of metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III criteria; and (3) simultaneous absence of metabolic abnormalities (diabetes, hypertension, dyslipidaemia).

Brain tissue- and cell type-specific eQTL Mendelian randomization reveals efficacy of FADS1 and FADS2 on cognitive function.

Epidemiological studies suggested an association between omega-3 fatty acids and cognitive function. However, the causal role of the fatty acid desaturase (FADS) gene, which play a key role in regulating omega-3 fatty acids biosynthesis, on cognitive function is unclear. Hence, we used two-sample Mendelian randomization (MR) to estimate the gene-specific causal effect of omega-3 fatty acids (N = 114,999) on cognitive function (N = 300,486).

Sex-stratified genome-wide association and transcriptome-wide Mendelian randomization studies reveal drug targets of heart failure.

The prevalence of heart failure (HF) subtypes, which are classified by left ventricular ejection fraction (LVEF), demonstrate significant sex differences. Here, we perform sex-stratified genome-wide association studies (GWASs) on LVEF and transcriptome-wide Mendelian randomization (MR) on LVEF, all-cause HF, HF with reduced ejection fraction (HFrEF), and HF with preserved ejection fraction (HFpEF). The sex-stratified GWASs of LVEF identified three sex-specific loci that were exclusively detected in the sex-stratified GWASs.

Small-molecule anti-COVID-19 drugs and a focus on China's homegrown mindeudesivir (VV116).

The coronavirus disease 2019 (COVID-19) pandemic has stimulated tremendous efforts to develop therapeutic agents that target severe acute respiratory syndrome coronavirus 2 to control viral infection. So far, a few small-molecule antiviral drugs, including nirmatrelvir-ritonavir (Paxlovid), remdesivir, and molnupiravir have been marketed for the treatment of COVID-19. Nirmatrelvir-ritonavir has been recommended by the World Health Organization as an early treatment for outpatients with mild-to-moderate COVID-19.

Branched-chain amino acid catabolic defect promotes α-cell proliferation via activating mTOR signaling.

Elevated circulating level of branched-chain amino acids (BCAAs) is closely related to the development of type 2 diabetes. However, the role of BCAA catabolism in various tissues in maintaining glucose homeostasis remains largely unknown. Pancreatic α-cells have been regarded as amino acid sensors in recent years.

Association of iron status with all-cause and cause-specific mortality in individuals with diabetes.

Aims: Current evidence regarding iron status and mortality risk among patients with diabetes is limited. This study aimed to evaluate association of iron indices with all-cause and cause-specific mortality risk among patients with diabetes.

Methods: The current study included 2080 (with ferritin data), 1974 (with transferrin saturation (Tsat) data), and 1106 (with soluble transferrin receptor (sTfR) data) adults with diabetes from NHANES 1999-2018.

FAP expression in adipose tissue macrophages promotes obesity and metabolic inflammation.

Adipose tissue macrophages (ATM) are key players in the development of obesity and associated metabolic inflammation which contributes to systemic metabolic dysfunction. We here found that fibroblast activation protein α (FAP), a well-known marker of cancer-associated fibroblast, is selectively expressed in murine and human ATM among adipose tissue-infiltrating leukocytes. Macrophage FAP deficiency protects mice against diet-induced obesity and proinflammatory macrophage infiltration in obese adipose tissues, thereby alleviating hepatic steatosis and insulin resistance.

Lipocalin 2-A bone-derived anorexigenic and β-cell promoting signal: From mice to humans.

The skeleton is traditionally known for its structural support, organ protection, movement, and maintenance of mineral homeostasis. Over the last 10 years, bone has emerged as an endocrine organ with diverse physiological functions. The two key molecules in this context are fibroblast growth factor 23 (FGF23), secreted by osteocytes, and osteocalcin, a hormone produced by osteoblasts.

Fecal short chain fatty acids modify therapeutic effects of sleeve gastrectomy.

Aims: We aimed to investigate changes of fecal short chain fatty acids (SCFAs) and their association with metabolic benefits after sleeve gastrectomy (SG). Specifically, whether pre-surgery SCFAs modify surgical therapeutic effects was determined.

Methods: 62 participants with measurements of fecal SCFAs and metabolic indices before and 1, 3, 6 months after SG were included.

A phenome-wide approach to identify causal risk factors for deep vein thrombosis.

Deep vein thrombosis (DVT) is the formation of a blood clot in a deep vein. DVT can lead to a venous thromboembolism (VTE), the combined term for DVT and pulmonary embolism, a leading cause of death and disability worldwide. Despite the prevalence and associated morbidity of DVT, the underlying causes are not well understood.

Early-life famine exposure, adulthood obesity patterns, and risk of low-energy fracture.

Malnutrition in early life increases the risk of osteoporosis, but the association of early-life undernutrition combined with adulthood obesity patterns with low-energy fracture remains unknown. This study included 5323 community-dwelling subjects aged ⩾40 years from China. Early-life famine exposure was identified based on the participants' birth dates.

Anti-infection effects of heparin on SARS-CoV-2 in a diabetic mouse model.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can result in more severe syndromes and poorer outcomes in patients with diabetes and obesity. However, the precise mechanisms responsible for the combined impact of corona virus disease 2019 (COVID-19) and diabetes have not yet been elucidated, and effective treatment options for SARS-CoV-2-infected diabetic patients remain limited. To investigate the disease pathogenesis, K18-hACE2 transgenic (hACE2 ) mice with a leptin receptor deficiency (hACE2-Lepr ) or high-fat diet (hACE2-HFD) background were generated.

Unlocking the Potential: Amino Acids' Role in Predicting and Exploring Therapeutic Avenues for Type 2 Diabetes Mellitus.

Diabetes mellitus, particularly type 2 diabetes mellitus (T2DM), imposes a significant global burden with adverse clinical outcomes and escalating healthcare expenditures. Early identification of biomarkers can facilitate better screening, earlier diagnosis, and the prevention of diabetes. However, current clinical predictors often fail to detect abnormalities during the prediabetic state.

Disruption of CerS6-mediated sphingolipid metabolism by FTO deficiency aggravates ulcerative colitis.

Background And Aims: Deregulation of RNA N6-methyladenosine (mA) modification in intestinal epithelial cells (IECs) influences intestinal immune cells and leads to intestinal inflammation. We studied the function of fat mass-and obesity-associated protein (FTO), one of the mA demethylases, in patients with ulcerative colitis (UC).

Methods: We analysed colon tissues of Fto; Villin-cre mice and their Fto littermates with dextran sulfate sodium (DSS) using real-time PCR and 16s rRNA sequencing.

Circ_072697 knockdown promotes advanced glycation end products-induced cell proliferation and migration in HaCaT cells via miR-3150a-3p/KDM2A axis.

Objective: Diabetes foot ulcer (DFU) is a serious complication of diabetes, which can lead to significant mortality and amputation rate. Our previous study found circ_072697 was highly expressed in DFU tissues, but the regulatory mechanism of circ_072697 in DFU remains unclear.

Methods: The relative expressions of circ_072697, miR-3150a-3p, and KDM2A in DFU patients or advanced glycation end products (AGEs)-treated HaCaT cells (used as DFU cell model) were determined by using qRT-PCR.

Diet-Related Lipidomic Signatures and Changed Type 2 Diabetes Risk in a Randomized Controlled Feeding Study With Mediterranean Diet and Traditional Chinese or Transitional Diets.

Objective: Few trials studied the links of food components in different diets with their induced lipidomic changes and related metabolic outcomes. Thus, we investigated specific lipidomic signatures with habitual diets and modified diabetes risk by using a trial and a cohort.

Research Design And Methods: We included 231 Chinese with overweight and prediabetes in a randomized feeding trial with Mediterranean, traditional, or transitional diets (control diet) from February to September 2019.

Association between serum LDL-C concentrations and risk of diabetes: A prospective cohort study.

Background: Low-density lipoprotein cholesterol (LDL-C) and diabetes mellitus are both modifiable risk factors for cardiovascular disease; however, whether elevated LDL-C levels confer a risk for diabetes remains unclear.

Objective: We aimed to examine the association between serum LDL-C concentrations at baseline and the risk of developing diabetes at follow-up in the general population of Chinese adults.

Methods: This study included 5274 adults aged ≥ 40 years from a community cohort who were without diabetes and followed for a median of 4.

The rs1421085 variant within FTO promotes brown fat thermogenesis.

One lead genetic risk signal of obesity-the rs1421085 T>C variant within the FTO gene-is reported to be functional in vitro but lacks evidence at an organism level. Here we recapitulate the homologous human variant in mice with global and brown adipocyte-specific variant knock-in and reveal that mice carrying the C-allele show increased brown fat thermogenic capacity and resistance to high-fat diet-induced adiposity, whereas the obesity-related phenotypic changes are blunted at thermoneutrality. Both in vivo and in vitro data reveal that the C-allele in brown adipocytes enhances the transcription of the Fto gene, which is associated with stronger chromatin looping linking the enhancer region and Fto promoter.

Systolic Blood Pressure Control Targets to Prevent Major Cardiovascular Events and Death in Patients With Type 2 Diabetes: A Systematic Review and Network Meta-Analysis.

Background: Previous meta-analyses using traditional pairwise comparisons did not support intensive systolic blood pressure (SBP) control in patients with diabetes and included trials published before 2015. We aimed to identify the optimal SBP control targets in patients with type 2 diabetes using a systematic review and network meta-analysis of accumulating evidence.

Methods: We systematically searched PubMed, Embase, and Cochrane Library from inception to August 29, 2022 for randomized controlled trials comparing different blood pressure targets, antihypertensive agents against placebo, or dual antihypertensive agents against single agent in patients with type 2 diabetes.

/β-catenin inactivation in UCP1-positive adipocytes augments the browning of white adipose tissue.

Canonical WNT pathway in mature adipocytes exacerbates obesity. In this study, we constructed UCP1-positive adipocytes-specific knockout mice (UBKO) and observed increased "browning" of white adipose tissue (WAT) following cold exposure or CL-316,243 administration compared to controls. UBKO mice also displayed increased energy expenditure.