This review assessed the role of Branched-Chain Amino Acid Transaminase (BCAT) enzymes in human metabolism, and their involvement in the catabolism of branched-chain amino acids (BCAAs) and exploring the association between Type 2 Diabetes Mellitus (T2DM) and Alzheimer's disease (AD) through insulin resistance.

The analysis involves a comprehensive literature review of recent research findings related to BCAT enzymes, BCAA metabolism, T2DM, and AD. Relevant studies and articles were identified through systematic searches in databases such as PubMed, ScienceDirect, and other scholarly resources. Inclusion criteria encompassed research articles, reviews, and studies published in peer-reviewed journals, with a focus on human metabolism, BCAT enzymes, and the interplay between BCAA metabolism, T2DM, and AD.

The association between T2DM and AD suggests a potential metabolic link, particularly through dysregulated BCAA metabolism leading to insulin resistance. The impact of impaired insulin signaling is implicated in brain function and the accumulation of amyloid plaques facilitated by BCAT.

The identified link between BCAT, BCAA metabolism, T2DM, and AD suggests that disruptions in BCAT levels could serve as valuable indicators for early detection of insulin resistance and cognitive impairment as observed in Type 3 Diabetes which may present a promising therapeutic target.

Triacylglycerol (TAG) plasma excursions after a high-fat meal are blunted after Roux-en-Y gastric bypass (RYGB), but underlying mechanisms are poorly understood. We studied TAG absorption and metabolism in 12 RYGB-operated individuals and 12 unoperated controls (CON) matched on sex, age, and BMI.

Participants followed a 7-day controlled diet and on day 4 underwent 1H-MR Spectroscopy of liver TAG and a high-fat liquid meal with oral and intravenous labeled stable isotope metabolites, subcutaneous abdominal fat biopsies, and indirect calorimetry. Subsequently, participants collected stool for 96 h.

Overall fat absorption from the controlled diet was moderately lower in RYGB than CON (88 % versus 93 %, P < 0.01), without indication of greater specific malabsorption of fat from the high-fat test meal (recovery of TAG and labeled TAG in 96-h stool samples). After an overnight fast, plasma TAG concentrations and incorporation of plasma fatty acids (IV tracer) into TAG did not differ between groups. The postprandial 6-h iAUC of plasma TAG plasma concentrations was markedly lower in RYGB than CON (15 versus 70 mmol/L × min, P = 0.03). The postprandial chylomicron (CM) particle response (plasma ApoB48) was initially higher in RYGB, but with lower CM-TAG plasma concentrations and appearance of labeled palmitate from the oral tripalmitin tracer over the 6 h.

Fat absorption is only moderately lower after RYGB compared with unoperated matched controls. Nevertheless, postprandial TAG and CM plasma kinetics after a high-fat meal are markedly altered after RYGB with substantially lower TAG and CM-TAG concentrations despite a faster CM particle release.

This study aimed to explore the effects of hypoglycemic agents with weight loss effect plus a high protein diet and moderate exercise on weight loss and diabetes remission in adults with obesity and newly diagnosed prediabetes/type 2 diabetes (T2D).

Participants with obesity and newly diagnosed prediabetes or T2D (n = 61) were randomly allocated to standard treatment group (conventional medication and lifestyle guidance for 12 months) and intensive treatment group (in addition to conventional medication, a high protein diet and moderate exercise were given for 12 months).

By month 12, 60 (98.4%) participants completed the 12-month follow-up visit. In the intensive treatment group, 73.33% patients in the prediabetes subgroup returned to normoglycemia and the diabetes remission rate was 86.67% in the diabetes subgroup, which were much higher than the remission rate of prediabetes subgroup (7.69%) and diabetes subgroup (16.67%) in the standard treatment group (P < 0.001). The mean weight change was - 19.29 kg (95% CI, - 22.95 to - 15.63) in the intensive treatment group and - 1.52 kg (95% CI, - 5.12 to 2.07) in the standard treatment group from baseline after intervention. The weight change between the two groups was significantly different (net difference, - 17.77 kg; 95% CI, - 22.90 to - 12.64; P < 0.001). Percent of body fat, visceral fat area, and hepatic controlled attenuation parameter value reduced significantly in the intensive treatment group compared to the standard treatment group (P < 0.001).

Hypoglycemic agents with weight loss effect plus a high protein diet and moderate exercise could lead to a considerable proportion of patients with diabetes achieving diabetes remission.

chictr.org.cn ChiCTR2100044305.

The long-term impact of the coronavirus disease 2019 (COVID-19) pandemic on metabolic risk factors in different populations has not been fully investigated. Insulin resistance (IR) is a cardinal risk factor for the development of type 2 diabetes mellitus. The current study sought to determine the prevalence and determinants of insulin resistance in selected Ghanaians with and without past COVID-19 status in the Cape Coast and Tamale metropolitan areas. Using a cross-sectional study design involving 510 adult participants, body mass index (BMI), waist-to-hip ratio, systolic blood pressure, lipid profile, insulin, plasma glucose, C-reactive protein (CRP), beta-cell function and insulin resistance levels were measured and compared between participants with and without past COVID-19 status. IR was determined by the homeostatic model (HOMA-IR) and the triglyceride-glucose index (TyG). Percentage prevalence and Poisson regression with prevalence ratio and 95% confidence intervals were applied. IR prevalence ranged from 70.69% to 79.09% (HOMA-IR) and 88.62% to 90.91% (TyG) respectively for Tamale and Cape Coast residents. IR prevalence values of 70.98% and 88% (HOMA-IR) and 89.02% and 90.2% (TyG) for without and with past COVID-19 groups respectively were observed. Irrespective of background, low (31.18%) and high (19.41%) levels of beta-cell function were detected. Additionally, high levels of very-low density lipoprotein cholesterol (8.31%), triglycerides (24.9%), total cholesterol (27.45%), low-density lipoprotein cholesterol (44.71%) and low level of high-density lipoprotein cholesterol (11.96%) coupled with low-grade inflammation (50.59%) were observed. Irrespective of surrogate marker used or past COVID-19 status, age, educational level and triglycerides could significantly associate with IR. With HOMA-IR, fasting plasma glucose, insulin and total cholesterol predicted IR in participants without prior COVID-19 status. With TyG, age, BMI, triglycerides and CRP were the predictors of IR in participants with past COVID-19 status. The risk of development of type 2 diabetes mellitus through insulin resistance is high in our setting. Measures to reduce the rising pace of IR are urgently needed in our setting.

Chronic inflammation in type 2 diabetes (T2D), characterized by constitutively activated immune cells and elevated pro-inflammatory mediators along with hyperglycaemia and increased free fatty acids and branched chain amino acid levels, significantly alters the immuno-metabolic axis. Over the years, dietary intervention has been explored as an effective strategy for managing T2D. Evidence from experimental and clinical studies indicates that various diets, including Mediterranean, Nordic, Palaeolithic and ketogenic diets, increase insulin sensitivity, decrease gluconeogenesis, and adiposity, and exert anti-inflammatory effects, thus preserving immuno-metabolic homeostasis in individuals with T2D. Indian dietary sources are categorized as Sattvic, Rajasic, and Tamasic, depending on their impact on health and behaviour. The Yogic diet, commonly recommended during yoga practice, is predominantly Sattvic, emphasizing plant-based whole foods while limiting processed and high-glycaemic-index items. Yogic diet is also recommended for Mitahara, emphasizing mindful eating, which is attributed to calorie restriction. Adopting a Yogic diet, featuring low-fat vegetarian principles, strongly reduces inflammatory mediator levels. This diet not only ameliorates insulin resistance and maintains a healthy body weight but also regulates immunomodulation, enhances gut microbiome diversity and provides essential phytonutrients, collectively preventing inflammation. Although, preliminary studies show aforementioned beneficial role of Yogic diet in improving diabetes associated metabolic and inflammatory changes, precise cellular and molecular mechanisms are not yet understood. Hence, further studies are warranted to decipher the mechanisms. This review summarizes the multiple roles of Yogic diet and related dietary components in mitigating inflammation and enhancing glycaemic control in T2D.

Chlorophyll-free fractions of Andrographis paniculata were investigated for glucose uptake and lipid reduction in 3T3-L1 adipocytes. At 25 µg/ml, the acid fraction concentration enhanced glucose uptake by 82%. Basic and neutral fractions at 100 µg/ml enhanced glucose uptake by 82% and 78%, respectively. The three fractions showed improved glucose uptake compared to the crude extract (25% uptake at 50 μg/ml). GC-MS analysis of the fractions revealed the presence of chemicals with antidiabetic activities. The neutral fraction was prioritised for pure compound isolation to provide known andrographolide (1), 14-deoxyandrographolide (2), and a novel compound, 3-epi-11,12-didehydro-14-deoxyandrographolide (5). At a concentration of 1 µM, compounds 2 and 5 are as effective as 10 mM metformin in glucose uptake. They also reduce lipid accumulations in 3T3-L1 adipocytes by decreasing the size and number of lipid droplets. The activities of fractions and compounds support the use of A. paniculata in treating type 2 diabetes.

Type 2 diabetes and obesity have some overlapping pathophysiology. This has allowed for the creation of therapies which are highly effective in treating both conditions. Weekly subcutaneous incretin agonists are preferred agents as they provide significant improvement in glycemic parameters, weight, and other comorbidities, like heart failure and reduce major adverse cardiovascular event. Bariatric surgery continues to show the most durable benefits for patients with both type 2 diabetes mellitus and obesity and should be considered in patients who are unable to meet goals with pharmacotherapy and lifestyle.

Cardiovascular-Kidney-Metabolic (CKM) syndrome typically commences with the interaction of insulin resistance (IR), excessive or dysfunctional obesity, and the consequent systemic inflammatory response and oxidative stress. The relationship between the triglyceride-glucose (TyG) index and TyG-related indices that may simply assess IR and obesity, as well as the mortality risk in the CKM syndrome population, remains ambiguous.

This study included 6,383 participants from the National Health and Nutrition Examination Survey (NHANES) 2009-2018. The TyG index, TyG-waist-to-height ratio (TyG-WHtR), TyG-waist circumference (TyG-WC), and TyG-body mass index (TyG-BMI) were developed. Cox proportional hazards models, smooth curve fitting, and two-stage Cox proportional hazards models were employed to examine the association of TyG and TyG-related indices with all-cause and cardiovascular mortality in the CKM syndrome population. Subgroup analyses and interaction tests were conducted to evaluate the risk within various demographics.

In survey-weighted multifactorial regression analyses, a significant positive association existed between TyG, TyG-related indices, and both all-cause mortality and cardiovascular mortality, except for the TyG index, which did not demonstrate a significant link with all-cause mortality. Of these indices, the TyG-WC index exhibited the strongest correlation with all-cause mortality, with a hazard ratio (HR) of 1.50 and a 95% confidence interval (CI) of 1.18-1.92, followed by the TyG-WHtR index (HR: 1.45, 95%CI 1.13-1.85). The TyG-WHtR index demonstrated the strongest correlation with cardiovascular mortality (HR: 1.85, 95% CI 1.19-2.86), followed by the TyG-WC index(HR: 1.83, 95%CI 1.21-2.78). An L-shaped association was identified between TyG-WHtR, TyG-BMI, and all-cause mortality in CKM syndrome during the examination of nonlinear relationships (both P for log-likelihood ratio < 0.05). The TyG-WHtR, TyG-WC, and TyG-BMI indices exhibited a more pronounced correlation with all-cause mortality in those with CKM syndrome stages 1 and 3 (P value < 0.05, P for interaction < 0.05).

Our study emphasizes the association between TyG and TyG-related indices and mortality in individuals with CKM syndrome stages 0-3. Individuals with CKM syndrome stages 1 and 3 should be more vigilant to abnormal alterations in TyG-related indices.

The visceral adiposity index (VAI) reflects changes in visceral adipose function and is also linked to cardiometabolic risk. The study aimed to investigate the association between VAI and both all-cause mortality and cardiovascular mortality in the U.S. population aged 20-65 years.

This study included data from 9,094 American adults aged 20-65 years from the 2009-2018 National Health and Nutrition Examination Survey (NHANES). The exposure variable was VAI, while the outcome variables were all-cause and cardiovascular mortality. The Cox regression model was employed to explore the correlation between VAI and mortality among participants. Restricted cubic splines (RCS) were used to explore the nonlinear associations, and a two-piecewise Cox proportional hazards model was applied on both sides of the inflection point. We used subgroup analyses and interaction tests to further investigate the association between VAI and mortality in different populations. Additionally, time-dependent Receiver Operating Characteristic (ROC) curve analyses were performed to evaluate the capability of VAI in forecasting survival.

During a median follow-up period of 74 months, 251 deaths from all causes and 50 cardiovascular-related deaths were recorded. RCS analyses did not find a nonlinear correlation between VAI and all-cause mortality (P for overall = 0.0006, P for nonlinear = 0.9927) but showed a nonlinear correlation with cardiovascular mortality (P for overall = 0.0010, P for nonlinear = 0.0062). For cardiovascular mortality, when VAI was below the threshold value (2.49), a significant positive association was observed with cardiovascular mortality. When VAI was below 2.49, the risk of cardiovascular mortality increased by 122 percent for each unit increase in VAI (HR=2.22, 95% CI:1.36-3.61). For VAI ≥ 2.49, changes in VAI did not significantly impact cardiovascular mortality risk. In subgroup analyses, the stratified results remained consistent, with no significant interactions observed in any of the subgroups (all P for interaction> 0.05). Furthermore, the areas under the curve (AUC) for 2-, 5-, and 10-year survival rates were 0.82, 0.80, and 0.79 for all-cause mortality and 0.86, 0.86, and 0.82 for cardiovascular mortality, respectively.

VAI was found to have a positive association with all-cause mortality and a nonlinear association with cardiovascular mortality in the non-elderly adults, with a threshold value of 2.49 for cardiovascular mortality.

Given the promising effects of GLP-1/GIP/glucagon receptor triagonists on weight loss in animals and humans, improved understanding of underlying mechanism is required. We investigated a direct lipolytic effect of a specific GLP-1/GIP/glucagon receptor triagonist on human adipose tissue to disentangle central and peripheral effects as potential drivers of weight loss.

Isolated primary adipocytes from subcutaneous adipose tissue biopsies of 22 non-diabetic subjects [63.0 (57.0-69.5) years] were incubated with increasing concentrations of isoprenaline, GLP-1, GIP, glucagon, or a GLP-1/GIP/glucagon receptor triagonist. Glycerol concentration was measured following stimulation to assess lipolysis. mRNA expression of adipose tissue receptors was analyzed in parallel.

Glycerol concentration only increased by isoprenaline, GIP (+13%), and GLP-1/GIP/glucagon receptor triagonist (+28%) but not by GLP-1 or glucagon. This effect was not related to age or body mass index (BMI). Higher adipose tissue GIP receptor mRNA expression was related to elevated glycerol release after GIP and GLP-1/GIP/glucagon receptor triagonist stimulation.

Direct lipolytic effects of GIP seem to exist in human subcutaneous adipose tissue. This might be targetable by multiple receptor agonists, especially with a high GIP receptor affinity. Such a mechanism can potentiate the beneficial effect on weight loss and will therefore represent a promising target of future research.

The trial was registered at German Clinical Trials Register (drks.de) as DRKS00010049.

Despite significant evidence on the anti-diabetic effect of chayote fruit and phenolic compounds, research on the mechanism of chayote (Sechium edule) pectin (CP) regulating blood glucose in type 2 diabetes mellitus (T2DM) is scarce. Therefore, this study aims to explore the potential mechanisms by which CP modulates blood glucose levels through an 8-week administration in db/db mice. The results showed that the CP treatment in db/db mice resulted in an elevation in glucagon-like peptide (GLP-1) secretion, an increase in hepatic glycogen storage, and a decrease in homeostasis model assessment-insulin resistance (HOMA-IR). Western blotting results showed that CP intervention significantly upregulated the expression of phosphatidylinositol 3 kinase (PI3K), phosphorylated protein kinase B (P-AKT) and downregulated the expression of fork-head transcription factor O1(FoxO1), glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK). Moreover, CP effectively upregulated the protein expression of hepatic G protein-coupled receptor 43 (GPR43) and phosphorylated adenosine 5'-monophosphate (AMP)-activated protein kinase (P-AMPK). Furthermore, CP rearranged the gut microbiota structure by increasing beneficial bacteria (unclassified_Ruminococcaceae, Muribaculaceae, Alloprevotella, Rikenella, and Parabacteroides) and reducing the Firmicutes/Bacteroidetes ratio. Additionally, CP improved the gut barrier by increasing the number and area of goblet cells and significantly upregulating the expression of Claudin-1 and Mucin-2. Overall, these findings suggest that CP regulated blood glucose by activating the gut-liver axis signaling pathway: gut microbiota/ SCFAs/ GLP-1, PI3K/AKT/FoxO1, and GPR43/AMPK/FoxO1. This study provides a scientific basis for the development and application of pectin-based functional foods.

Exercise provides health benefits to multiple metabolic tissues through complex biological pathways and interactions between organs. However, investigating these complex mechanisms in humans is still limited, making mouse models extremely useful for exploring exercise-induced changes in whole-body metabolism and health. In this review, we focus on gaining a broader understanding of the metabolic phenotypes and molecular mechanisms induced by exercise in mouse models. We first discuss the differences in adaptations induced by aerobic and resistance exercise, and compare voluntary wheel running and forced treadmill exercise, the two main methods of aerobic exercise research in mice, to show the similarities and differences between the same aerobic exercise but different methods, and their impact on experimental outcomes. The effects of exercise on metabolic phenotypes, including alleviation of obesity and metabolic disorders, and the mechanisms involved in adipose tissue remodelling and browning are explored, as well as the role of the gut microbiota in mediating the physiological responses and metabolic effects of exercise. Understanding these molecular mechanisms and methodological aspects of exercise experiments in mouse models can serve as a valuable template for the design of future basic research in exercise physiology and will provide a strong scientific evidence base for optimizing the design of exercise intervention programmes for metabolic health.

Type 2 diabetes mellitus (T2DM) is not just a local health issue but a significant global health burden, affecting patient outcomes and clinical management worldwide. Despite the wealth of studies reporting T2DM biomarkers, there is an urgent need for a comparative review. This review aims to provide a comprehensive analysis based on the reported T2DM biomarkers and how these are linked with other conditions, such as inflammation and wound healing. A comparative review was conducted on 24 001 study participants, including 10 024 T2DM patients and 13 977 controls (CTL; age 30-90 years). Four main profiles were extracted and analysed from the clinical reports over the past 11 years: haematological (1084 cases vs. 1458 CTL), protein (6753 cases vs. 9613 CTL), cytokine (975 cases vs. 1350 CTL) and lipid (1212 cases vs. 1556 CTL). This review provides a detailed analysis of the haematological profile in T2DM patients, highlighting fundamental changes such as increased white blood cells and platelet counts, accompanied by decreases in red blood cell counts and iron absorption. In the serum protein profile, a reduction in albumin and anti-inflammatory cytokines was noted along with an increase in globulin levels and pro-inflammatory cytokines. Furthermore, changes in lipid profiles were discussed, specifically the decreases in high-density lipoprotein (HDL) and the increases in low-density lipoprotein (LDL) and triglycerides. Understanding the changes in these four biomarker profiles is essential for developing innovative strategies to create diagnostic and prognostic tools for diabetes management.

Metabolic syndrome (MS) represents a complex cluster of metabolic disorders primarily characterized by obesity, insulin resistance, hyperglycemia, dyslipidemia, hypertension, and hyperuricemia. Diet and functional ingredients play a pivotal role in seeking non-pharmacological strategies to prevent and ameliorate MS. Astaxanthin (AST), a carotenoid found in various marine organisms, exhibits exceptional antioxidant properties and holds great promise as a natural compound that improves MS. This article introduces the basic properties of AST, including its absorptance and metabolic pathways, along with various isomers. Most importantly, we comprehensively review the effects and mechanisms of AST on improving the primary components of MS. These mechanisms primarily involve regulating signal transduction, transport, or metabolic pathways within the body, as well as influencing intestinal microbiota and metabolites, thereby exerting positive effects on metabolism and inhibiting the occurrence of MS. This review emphasizes the potential efficacy of AST in managing MS. However, more studies are needed to confirm the clinical effect of AST on MS and reveal potential molecular mechanisms.

Metabolic syndrome (MetS) is an indicator and diverse endocrine syndrome that combines different metabolic defects with clinical, physiological, biochemical, and metabolic factors. Obesity, visceral adiposity and abdominal obesity, dyslipidemia, insulin resistance (IR), elevated blood pressure, endothelial dysfunction, and acute or chronic inflammation are the risk factors associated with MetS. Abdominal obesity, a hallmark of MetS, highlights dysfunctional fat tissue and increased risk for cardiovascular disease and diabetes. Insulin, a vital peptide hormone, regulates glucose metabolism throughout the body. When cells become resistant to insulin's effects, it disrupts various molecular pathways, leading to IR. This condition is linked to a range of disorders, including obesity, diabetes, fatty liver disease, cardiovascular disease, and polycystic ovary syndrome. Atherogenic dyslipidemia is characterized by three key factors: high levels of small, low-dense lipoprotein (LDL) particles and triglycerides, alongside low levels of high-density lipoprotein (HDL), the "good" cholesterol. Such a combination is a major player in MetS, where IR is a driving force. Atherogenic dyslipidemia contributes significantly to the development of atherosclerosis, which can lead to cardiovascular disease. On top of that, genetic alteration and lifestyle factors such as diet and exercise influence the complexity and progression of MetS. To enhance our understanding and consciousness, it is essential to understand the fundamental pathogenesis of MetS. This review highlights current advancements in MetS research including the involvement of gut microbiome, epigenetic regulation, and metabolomic profiling for early detection of Mets. In addition, this review emphasized the epidemiology and fundamental pathogenesis of MetS, various risk factors, and their preventive measures. The goal of this effort is to deepen understanding of MetS and encourage further research to develop effective strategies for preventing and managing complex metabolic diseases.

Metabolic dysfunction-associated steatotic liver disease/steatohepatitis (MASLD/MASH) is recognised as a metabolic disease characterised by excess intrahepatic lipid accumulation due to lipid overflow and synthesis, alongside impaired oxidation and/or export of these lipids. But where do these lipids come from? The main pathways related to hepatic lipid accumulation are de novo lipogenesis and excess fatty acid transport to the liver (due to increased lipolysis, adipose tissue insulin resistance, as well as excess dietary fatty acid intake, in particular of saturated fatty acids). Not only triglycerides but also other lipids are secreted by the liver and are associated with a worse histological profile in MASH, as shown by lipidomics. Herein, we review the role of lipid metabolism in MASLD/MASH and discuss the impact of weight loss (diet, bariatric surgery, GLP-1RAs) or other pharmacological treatments (PPAR or THRβ agonists) on hepatic lipid metabolism, lipidomics, and the resolution of MASH.

Sarcopenia is a progressive muscle wasting disorder that severely impacts the quality of life of elderly individuals. Although the natural aging process primarily causes sarcopenia, it can develop in response to other conditions. Because muscle function is influenced by numerous changes that occur with age, the etiology of sarcopenia remains unclear. However, recent characterizations of the aging muscle transcriptional landscape, signaling pathway disruptions, fiber and extracellular matrix compositions, systemic metabolomic and inflammatory responses, mitochondrial function, and neurological inputs offer insights and hope for future treatments. This review will discuss age-related changes in healthy muscle and our current understanding of how this can deteriorate into sarcopenia. As our elderly population continues to grow, we must understand sarcopenia and find treatments that allow individuals to maintain independence and dignity throughout an extended lifespan.

This research seeks to examine the correlation between the triglyceride-glucose index and the hazard of all-cause and cardiovascular death in individuals with cardiovascular disease (CVD). By evaluating the index, we can better anticipate and assess the risk and prognosis of CVD patients, and provide precise and individualized guidance for clinical treatment and management. Demographic and clinical data of 2185 CVD patients from 10 cycles of the National Health and Nutrition Examination Survey database from 1999 to 2018 were extracted for analysis. Employed the 3-level quantile method to group data, and a multivariate Cox proportional hazard model along with subgroup analysis to study the correlation between index and both mortalities. Additionally, restricted cubic spline examination was employed to assess the correlation, aiming to enhance the comprehension of their interrelation. Over the course of an average post-observation duration of 89.5 months involving 2185 CVD individuals, 607 patients suffered from all-cause mortality and 313 patients suffered from CVD-related mortality. An inverted U-shaped correlation was identified through restricted cubic spline analysis. During the multivariate COX regression analysis, it was found that individuals in the T2 and T3 had a dramatically lower hazard of both mortalities as opposed to those in the T1. The results were overall consistent across subgroup analyses according to age, gender, race, body mass index, diabetes, and hypertension, the interaction between these characteristics and the index was not remarkable (P > .05). Studies conducted on CVD individuals in the US have revealed a U-shaped correlation between triglyceride-glucose index and hazard of both all-cause and CVD-related death. However, further investigations are required to examine the particular function of index in forecasting the prognosis of CVD individuals. This will be helpful in accurately evaluating the risk and prognosis of CVD patients, and ultimately in developing more precise and personalized treatment and management strategies.

Fasting hypoglycemia is a severe and incompletely understood symptom of various inborn errors of metabolism (IEM). Precision-cut liver slices (PCLS) represent a promising model for studying glucose production ex vivo. This study quantified the net glucose production of human and murine PCLS in the presence of different gluconeogenic precursors. Dihydroxyacetone-supplemented slices from the fed mice yielded the highest rate, further stimulated by forskolin and dibutyryl-cAMP. Moreover, using 13C isotope tracing, we assessed the contribution of glycogenolysis and gluconeogenesis to net glucose production over time. Pharmacological inhibition of the glucose 6-phosphate transporter SLC37A4 markedly reduced net glucose production and increased lactate secretion and glycogen storage, while glucose production was completely abolished in PCLS from glycogen storage disease type Ia and Ib patients. In conclusion, this study identifies PCLS as an effective ex vivo model to study hepatic glucose production and opens opportunities for its future application in IEM research and beyond.

Insulin resistance (IR) is a key feature of type 2 diabetes (T2D) and an independent risk factor for metabolic syndrome. Previous studies have linked elevated serum uric acid (SUA) to an increased risk of T2D.

The purpose of this study was to investigate the relationship between SUA and IR. At the same time, the correlation between New model and SUA compared with other IR alternatives was compared, so as to provide a simple and effective new indicator for early detection and prediction of IR risk and early prevention of T2D.

The first cohort was the Discovery Cohort, which included 318 obese patients. And the second cohort was the Verification Cohort, which included a total of 4333 subjects who underwent a routine health checkup at our hospital. Spearman correlation analysis and binary logistic regression analysis were used to discuss the correlation between SUA and IR.

Regardless of sex, fasting insulin (FINS) and IR replacement markers increased with SUA (P<0.001). In both cohorts, SUA was associated with IR alternatives, especially with New model, and differed between men and women in all correlation analyses. After adjusting for confounding factors, SUA was still associated with IR (P<0.001).

The correlation between SUA and IR was significantly stronger in women than in men. And the correlation between SUA and New model is stronger than other IR replacement models. However, the causal relationship between SUA and IR has not been clearly established.

The mitochondrial pyruvate carrier (MPC) occupies a critical node in intermediary metabolism, prompting interest in its utility as a therapeutic target for the treatment of obesity and cardiometabolic disease. Dysregulated nutrient metabolism in adipose tissue is a prominent feature of obesity pathophysiology, yet the functional role of adipose MPC has not been explored. We investigated whether the MPC shapes the adaptation of adipose tissue to dietary stress in female and male mice.

The impact of pharmacological and genetic disruption of the MPC on mitochondrial pathways of triglyceride assembly (lipogenesis and glyceroneogenesis) was assessed in 3T3L1 adipocytes and murine adipose explants, combined with analyses of adipose MPC expression in metabolically compromised humans. Whole-body and adipose-specific glucose metabolism were subsequently investigated in male and female mice lacking adipocyte MPC1 (Mpc1AD-/-) and fed either standard chow, high-fat western style, or high-sucrose lipid restricted diets for 24 weeks, using a combination of radiolabeled tracers and GC/MS metabolomics.

Treatment with UK5099 or siMPC1 impaired the synthesis of lipids and glycerol-3-phosphate from pyruvate and blunted triglyceride accumulation in 3T3L1 adipocytes, whilst MPC expression in human adipose tissue was negatively correlated with indices of whole-body and adipose tissue metabolic dysfunction. Mature adipose explants from Mpc1AD-/- mice were intrinsically incapable of incorporating pyruvate into triglycerides. In vivo, MPC deletion restricted the incorporation of circulating glucose into adipose triglycerides, but only in female mice fed a zero fat diet, and this associated with sex-specific reductions in tricarboxylic acid cycle pool sizes and compensatory transcriptional changes in lipogenic and glycerol metabolism pathways. However, whole-body adiposity and metabolic health were preserved in Mpc1AD-/- mice regardless of sex, even under conditions of zero dietary fat.

These findings highlight the greater capacity for mitochondrially driven triglyceride assembly in adipose from female versus male mice and expose a reliance upon MPC-gated metabolism for glucose partitioning in female adipose under conditions of dietary lipid restriction.

The functional differences between preadipocytes and fully differentiated mature adipocytes derived from stromal vascular fraction stem cells, as well as primary adipocytes have been analysed by evaluating their response to the obesogenic factor (a saturated fatty acid) and TNF-triggered inflammation. The analysis of single adipocytes shows that the saturated fatty acid (palmitic acid) accumulation is accompanied by inflammation and considerably dependent on the stage of the adipogenesis. In particular, preadipocytes show the exceptional potential for palmitic acid uptake resulting in their hypertrophy and the elevated cellular expression of the inflammation marker (ICAM-1). Our research provides new information on the impact of obesogenic factors on preadipocytes that is important in the light of childhood obesity prevention.

The proportion of young Japanese women who are underweight is exceptionally high. We previously showed that the prevalence of impaired glucose tolerance (IGT) was high in underweight young Japanese women, and that IGT was characterized by high free fatty acid levels and adipose tissue insulin resistance (ATIR). As the next step, this study aimed to explore factors associated with elevated ATIR in this population.

Ninety-eight young, healthy, underweight women participated in this study.

To investigate the relationship between ATIR and metabolic parameters, participants were divided into three groups (Low, Medium, and High) according to ATIR level. Body composition examination, oral glucose tolerance testing, and blood biochemical analysis were performed; Adipo-IR and the Matsuda index were used as indices of ATIR and systemic insulin sensitivity, respectively.

Participants in the High ATIR group had the highest prevalence of IGT (25%), and significantly higher body fat percentage, whole-body insulin resistance, and levels of insulin-like growth factor-1 and dehydroepiandrosterone sulfate (DHEA-S) than the other two groups. They were also significantly younger and had higher systolic blood pressure than the Low ATIR group. Multiple regression analysis showed that DHEA-S, which is known to enhance lipolysis in adipose tissue, was an independent correlate of ATIR.

Underweight Japanese women with high ATIR had impaired metabolism, a higher prevalence of IGT, higher systemic insulin resistance, and higher systolic blood pressure. DHEA-S was a determinant of high ATIR levels.

Obesity rates have nearly tripled in the past 50 years, and by 2030 more than 1 billion individuals worldwide are projected to be obese. This creates a significant economic strain due to the associated non-communicable diseases. The root cause is an energy expenditure imbalance, owing to an interplay of lifestyle, environmental, and genetic factors. Obesity has a polygenic genetic architecture; however, single genetic variants with large effect size are etiological in a minority of cases. These variants allowed the discovery of novel genes and biology relevant to weight regulation and ultimately led to the development of novel specific treatments.

We used a case-control approach to determine metabolic differences between individuals homozygous for a loss-of-function genetic variant in the small integral membrane protein 1 (SMIM1) and the general population, leveraging data from five cohorts. Metabolic characterization of SMIM1-/- individuals was performed using plasma biochemistry, calorimetric chamber, and DXA scan.

We found that individuals homozygous for a loss-of-function genetic variant in SMIM1 gene, underlying the blood group Vel, display excess body weight, dyslipidemia, altered leptin to adiponectin ratio, increased liver enzymes, and lower thyroid hormone levels. This was accompanied by a reduction in resting energy expenditure.

This research identified a novel genetic predisposition to being overweight or obese. It highlights the need to investigate the genetic causes of obesity to select the most appropriate treatment given the large cost disparity between them.

This work was funded by the National Institute of Health Research, British Heart Foundation, and NHS Blood and Transplant.

Free Fatty Acids (FFAs) are vital for energy homeostasis and the pathogenesis of a variety of diseases, including diabetes. For the first time, we presumed and investigated the types and levels of FFAs and their links to Insulin Resistance (IR) and Oxidative Stress (OS) in T2DM. A case-control study was conducted on 60 individuals with diabetes, 60 prediabetics with IFG, and 60 control groups. A Gas Chromatography Flame Ionization Detector (GC-FID) was used to estimate FFAs, which were then classified based on length and saturation. Indeed, antioxidant parameters such as TAC, MDA levels, PON-1, SOD-3, and CAT activity were assessed. Higher levels of LCFFA, SFFA, USFFA, and total FFA were found in people with diabetes and prediabetes. These levels were also linked to higher levels of HOMA-IR, BMI, FBS, HbA1C, and MDA, but lower levels of antioxidants. Furthermore, adjusting the above FFAs with age, sex, and antihypertensive medication increased T2DM development. SCFFA and ω3/6 fatty acids had a negative relationship with HOMA-IR, FBS, and insulin and a positive relationship with TAC. Adjusted SCFFA reduces T2DM risk. According to our models, total FFA is utilized to diagnose diabetes (AUC = 83.98, cut-off > 919 μM) and SCFFA for prediabetes (AUC = 82.32, cut-off < 39.56 μM). Total FFA (≥ 776 μM), LCFFA (≥ 613 μM), SFFA (≥ 471 μM), and USFFA (≥ 398 μM) all increase the risk of T2DM by increasing OS, BMI, and HOMA-IR. On the other hand, SCFFAs (≥ 38.7 μM) reduce the risk of T2DM by reducing BMI, HOMA-IR, and OS. SCFFAs and total FFAs can be used for the diagnosis of prediabetes and diabetes, respectively.

The relationship of adipose tissue insulin resistance (AT-IR, a product of fasting insulin and free fatty acids) and homeostasis-model assessment-insulin resistance (HOMA-IR) to β-cell function was studied cross-sectionally in the setting of subtle glucose dysregulation. Associations of AT-IR and HOMA-IR with fasting and post-glucose glycemia and β-cell function inferred from serum insulin kinetics during a 75 g oral glucose tolerance test were studied in 168 young female Japanese students. β-cell function was evaluated by disposition index calculated as a product of the insulinogenic index (IGI) and Matsuda index. AT-IR, not HOMA-IR, showed positive associations with post-glucose glycemia and area under the glucose response curve although both indices were associated with fasting glycemia. HOMA-IR, not AT-IR, was associated positively with log IGI whereas both indices were inversely associated with Matsuda index. AT-IR, not HOMA-IR, showed inverse associations with log disposition index. Associations of adipose tissue insulin resistance with β-cell function (inverse) and glucose excursion in young Japanese women may suggest that lipotoxicity to pancreatic β-cells for decades may be associated with β cell dysfunction found in Japanese patients with type 2 diabetes. Positive association of HOMA-IR with insulinogenic index may be associated with compensatory increased insulin secretion.

To determine whether alterations in nonesterified fatty acid (NEFA) dynamics or degree of hyperandrogenism (HA) contribute to the difference in insulin sensitivity between women with metabolically healthy obese polycystic ovary syndrome (PCOS) (MHO-PCOS) and women with metabolically unhealthy obese PCOS (MUO-PCOS).

Prospective cross-sectional study.

Tertiary-care academic center.

One hundred twenty-five obese women with PCOS.

Consecutive obese (body mass index [BMI] ≥ 30 kg/m2) oligo-ovulatory women (n = 125) with PCOS underwent an oral glucose tolerance test and a subgroup of 16 participants underwent a modified frequently sampled intravenous glucose tolerance test to determine insulin-glucose and -NEFA dynamics.

Degree of insulin resistance (IR) in adipose tissue (AT) basally (Adipo-IR) and dynamically (the nadir in NEFA levels observed [NEFAnadir], the time it took for NEFA levels to reach nadir [TIMEnadir], and the percent suppression in plasma NEFA levels from baseline to nadir [%NEFAsupp]); peak lipolysis rate (SNEFA) and peak rate of NEFA disposal from plasma pool (KNEFA); whole-body insulin-glucose interaction (acute response of insulin to glucose [AIRg], insulin sensitivity index [Si], glucose effectiveness [Sg], and disposition index [Di]); and HA (hirsutism score, total and free testosterone levels, and dehydroepiandrosterone sulfate levels).

A total of 85 (68%) women were MUO-PCOS and 40 (32%) were MHO-PCOS using the homeostasis model of assessment of IR. Subjects with MUO-PCOS and MHO-PCOS did not differ in mean age, BMI, waist-to-hip ratio, HA, and lipoprotein levels. By a modified frequently sampled intravenous glucose tolerance test, eight women with MUO-PCOS had lesser Si, KNEFA, and the percent suppression in plasma NEFA levels from baseline to nadir (%NEFAsupp) and greater TIMEnadir, NEFAnadir, and baseline adipose tissue IR index (Adipo-IR) than eight subjects with MHO-PCOS, but similar fasting NEFA levels and SNEFA. Women with MUO-PCOS had a higher homeostasis model of assessment-β% and fasting insulin levels than women with MHO-PCOS. In bivalent analysis, Si correlated strongly and negatively with Adipo-IR and NEFAnadir, weakly and negatively with TIMEnadir, and positively with KNEFA and %NEFAsupp, in women with MUO-PCOS only.

Independent of age and BMI, women with MUO-PCOS have reduced NEFA uptake and altered insulin-mediated NEFA suppression, but no difference in HA, compared with women with MHO-PCOS. Altered insulin-mediated NEFA suppression, rather than HA or lipolysis rate, contributes to variations in insulin sensitivity among obese women with PCOS.

Diameter, plaque score, and resistance index (RI) in the common carotid artery (CCA) are indicators of arterial remodeling, atherosclerosis, and vascular resistance, respectively. This study investigated the longitudinal association between adipose tissue insulin resistance or serum free fatty acid (FFA) levels and the CCA parameters.

This retrospective cohort analysis included 1089 participants (mean age 57.6 years; 40.0 % women) with data on health checkups from January 1982 to March 2003 and carotid artery ultrasonography from January 2015 to June 2019. Baseline serum FFA and immunoreactive insulin levels were assessed before and 30, 60, and 120 min after glucose ingestion. Adipose insulin resistance index (Adipo-IR) was calculated as the product of fasting serum insulin and FFA levels. An RI value >0.75 was defined as high RI.

A significant association was found between Adipo-IR and RI; however, Adipo-IR showed no association with CCA diameter or plaque score. The incidence of high RI increased with Adipo-IR quartile (Q) groups (47.3 % in Q1, 52.8 % in Q2, 53.3 % in Q3, 62.4 % in Q4; Cochrane-Armitage test for trend, p < 0.001). In multivariate analysis, Adipo-IR levels (Q4 vs. Q1 odds ratio: 1.67, 95 % confidence interval: 1.12-2.51) were positively associated with high RI incidence. Moreover, a significant association was found between RI and serum FFA levels after glucose intake, but not fasting FFA levels.

Future vascular resistance was predicted by insulin resistance in the adipose tissue. After glucose intake, serum FFA levels may significantly impact vascular resistance development.

The mitochondrial pyruvate carrier (MPC) occupies a critical node in intermediary metabolism, prompting interest in its utility as a therapeutic target for the treatment of obesity and cardiometabolic disease. Dysregulated nutrient metabolism in adipose tissue is a prominent feature of obesity pathophysiology, yet the functional role of adipose MPC has not been explored. We investigated whether the MPC shapes the adaptation of adipose tissue to dietary stress in female and male mice.

The impact of pharmacological and genetic disruption of the MPC on mitochondrial pathways of triglyceride assembly (lipogenesis and glyceroneogenesis) was assessed in 3T3L1 adipocytes and murine adipose explants, combined with analyses of adipose MPC expression in metabolically compromised humans. Whole-body and adipose-specific glucose metabolism were subsequently investigated in male and female mice lacking adipocyte MPC1 (Mpc1AD-/-) and fed either standard chow, high-fat western style, or high-sucrose lipid restricted diets for 24 weeks, using a combination of radiolabeled tracers and GC/MS metabolomics.

Treatment with UK5099 or siMPC1 impaired the synthesis of lipids and glycerol-3-phosphate from pyruvate and blunted triglyceride accumulation in 3T3L1 adipocytes, whilst MPC expression in human adipose tissue was negatively correlated with indices of whole-body and adipose tissue metabolic dysfunction. Mature adipose explants from Mpc1AD-/- mice were intrinsically incapable of incorporating pyruvate into triglycerides. In vivo, MPC deletion restricted the incorporation of circulating glucose into adipose triglycerides, but only in female mice fed a zero fat diet, and this associated with sex-specific reductions in tricarboxylic acid cycle pool sizes and compensatory transcriptional changes in lipogenic and glycerol metabolism pathways. However, whole-body adiposity and metabolic health were preserved in Mpc1AD-/- mice regardless of sex, even under conditions of zero dietary fat.

These findings highlight the greater capacity for mitochondrially driven triglyceride assembly in adipose from female versus male mice and expose a reliance upon MPC-gated metabolism for glucose partitioning in female adipose under conditions of dietary lipid restriction.

Interleukin-27 (IL-27), a potential mediator linking obesity to inflammatory diseases, is considered an important candidate for regulating obesity. The present study evaluated the relationship of IL-27 with obesity and insulin resistance (IR) and further investigated the changes in IL-27 levels after weight loss.

The study analyzed 405 participants, of whom 62 with overweight or obesity completed one year of lifestyle intervention. The body compositions, including percent of body fat (PBF), visceral fat area (VFA), skeletal muscle mass (SMM), and visceral fat area to skeletal muscle mass ratio (VSR), were assessed using the bioelectrical impedance analysis method. Serum IL-27 levels were measured using the enzyme-linked immunosorbent assay (ELISA).

IL-27 levels increased significantly with the increase in body mass index (BMI) (P < 0.001). Moreover, IL-27 levels were positively correlated with PBF, VFA, and VSR. Homeostatic model assessment for insulin resistance (HOMA-IR), the inverse of hepatic insulin sensitivity (1/HISI), adipose tissue insulin resistance (Adipo-IR), and homeostasis model assessment-adiponectin (HOMA-AD) increased significantly with each quartile of IL-27 levels (all P < 0.001). IL-27 levels significantly decreased after weight loss (P < 0.001).

IL-27 was positively correlated with obesity, HOMA-IR, 1/HISI, Adipo-IR, and HOMA-AD. IL-27 levels significantly decreased after weight loss.

The Metabolic Score for Insulin Resistance (METS-IR) offers a promising and reliable non-insulin-based approach to assess insulin resistance and evaluate cardiometabolic risk. However, evidence for the association between METS-IR and hypertension was still limited.

Participants from the National Health and Nutrition Examination Survey (NHANES) database from 2007-2016 were selected for weighted multivariable regression analyses, subgroup analyses and restricted cubic spline (RCS) modeling to assess the association between the METS-IR and hypertension, as well as systolic blood pressure (SBP) and diastolic blood pressure (DBP).

This study enrolled 7,721 adults aged ≥20 years, 2,926 (34.03%) of whom was diagnosed as hypertension. After adjusting for all potential covariates, an increased METS-IR (log2 conversion, denoted as log2METS-IR) was independently associated with a higher prevalence of hypertension (odd ratio [OR] 3.99, 95% confidence interval [CI] 3.19~5.01). The OR for hypertension in subjects with the highest quartile of METS-IR was 3.89-fold (OR 3.89, 95% CI 3.06~4.94) higher than that in those with the lowest quartile of METS-IR. This positive correlation became more significant as METS-IR increased (p for trend < 0.001). Log2METS-IR was significantly correlated with increase in SBP (β 6.75, 95% CI 5.65~7.85) and DBP (β 5.59, 95% CI 4.75~6.43) in a fully adjusted model. Consistent results were obtained in subgroup analyses. Hypertension, SBP and DBP all exhibited a non-linear increase with the rise in METS-IR. The minimal threshold for the beneficial association of METS-IR with hypertension, SBP and DBP were all identified to be 46.88.

The findings of this study revealed a significant positive association between METS-IR and hypertension among US adults, suggesting METS-IR as a potential tool for assessing hypertension risk.

Adipose organ, historically known as specialized lipid-handling tissue serving as the long-term fat depot, is now appreciated as the largest endocrine organ composed of two main compartments, i.e., subcutaneous and visceral adipose tissue (AT), madding up white and beige/brown adipocytes. Adipose organ dysfunction manifested as maldistribution of the compartments, hypertrophic, hypoxic, inflamed, and insulin-resistant AT, contributes to the development of type 2 diabetes (T2D). Here, we highlight the role of nitric oxide (NO·) in AT (dys)function in relation to developing T2D. The key aspects determining lipid and glucose homeostasis in AT depend on the physiological levels of the NO· produced via endothelial NO· synthases (eNOS). In addition to decreased NO· bioavailability (via decreased expression/activity of eNOS or scavenging NO·), excessive NO· produced by inducible NOS (iNOS) in response to hypoxia and AT inflammation may be a critical interfering factor diverting NO· signaling to the formation of reactive oxygen and nitrogen species, resulting in AT and whole-body metabolic dysfunction. Pharmacological approaches boosting AT-NO· availability at physiological levels (by increasing NO· production and its stability), as well as suppression of iNOS-NO· synthesis, are potential candidates for developing NO·-based therapeutics in T2D.

Adipocyte hypertrophy is associated with metabolic complications independent of obesity. We aimed to determine: 1) the association between adipocyte size and postprandial fatty acid metabolism; 2) the potential mechanisms driving the obesity-independent, hypertrophy-associated dysmetabolism in vivo and at a single-cell resolution. Tracers with positron emission tomography were used to measure fatty acid metabolism in 40 men and women with normal or impaired glucose tolerance (NCT02808182), and single nuclei RNA-sequencing (snRNA-seq) to determine transcriptional dynamics of subcutaneous adipose tissue (AT) between individuals with AT hypertrophy vs. hyperplasia matched for sex, ethnicity, glucose-tolerance status, BMI, total and percent body fat, and waist circumference. Adipocyte size was associated with high postprandial total cardiac fatty acid uptake and higher visceral AT dietary fatty acid uptake, but lower lean tissue dietary fatty acid uptake. We found major shifts in cell transcriptomal dynamics with AT hypertrophy that were consistent with in vivo metabolic changes.

The impact of insulin, particularly exogenous hyperinsulinemia, on insulin secretion in humans is debated.

We assessed the effects of exogenous hyperinsulinemia on insulin secretion and whether the response is altered in insulin resistance associated with obesity.

Insulin secretion rates (ISRs) during euglycemic hyperinsulinemic clamp studies (52 volunteers) were calculated using a model that employs plasma C-peptide concentrations. One study involved a 2-step insulin clamp and the other study was a single step insulin clamp. For both studies the goal was to achieve plasma glucose concentrations of 95 mg/dL during the clamp irrespective of fasting glucose concentrations. The percent change in ISR from fasting to the end of the insulin clamp interval was the main outcome. Linear regression and analysis of covariance were used to test for the effects of insulin on ISR and to test for group differences.

ISR was greater in obese volunteers (P < .001) under fasting and hyperinsulinemic clamp conditions. The change in plasma glucose from baseline to the end of the insulin clamp interval was highly correlated with the change in ISR (r = 0.61, P < .001). From baseline to the end of the clamp we observed a 27% (SD 20) suppression of ISR. The participants who underwent a 2-step insulin clamp had greater suppression of ISR during the second step than the first step (P < .001). The proportional suppression of ISR during euglycemic hyperinsulinemia was not different between nonobese and obese groups (P = .19).

Hyperinsulinemia suppresses endogenous insulin secretion and the relative change in insulin secretion produced by exogenous insulin did not differ between nonobese and obese people.

The ratio of free fatty acid (FFA) turnover decreases significantly with the expansion of white adipose tissue. Adipose tissue and dietary saturated fatty acid levels significantly correlate with an increase in fat cell size and number. The G0/G1 switch gene 2 increases lipid content in adipocytes and promotes adipocyte hypertrophy through the restriction of triglyceride (triacylglycerol: TAG) turnover. Hypoxia in obese adipose tissue due to hypertrophic adipocytes results in excess deposition of extracellular matrix (ECM) components. Cluster of differentiation (CD) 44, as the main receptor of the extracellular matrix component regulates cell-cell and cell-matrix interactions including diet-induced insulin resistance. Excess TAGs, sterols, and sterol esters are surrounded by the phospholipid monolayer surface and form lipid droplets (LDs). Once LDs are formed, they grow up because of the excessive amount of intracellular FFA stored and reach a final size. The ratio of FFA turnover/lipolysis decreases significantly with increases in the degree of obesity. Dysfunctional adipose tissue is unable to expand further to store excess dietary lipids, increased fluxes of plasma FFAs lead to ectopic fatty acid deposition and lipotoxicity. Reduced neo-adipogenesis and dysfunctional lipid-overloaded adipocytes are hallmarks of hypertrophic obesity linked to insulin resistance. Obesity-associated adipocyte death exhibits feature of necrosis-like programmed cell death. Adipocyte death is a prerequisite for the transition from hypertrophic to hyperplastic obesity. Increased adipocyte number in obesity has life-long effects on white adipose tissue mass. The positive correlation between the adipose tissue volume and magnetic resonance imaging proton density fat fraction estimation is used for characterization of the obesity phenotype, as well as the risk stratification and selection of appropriate treatment strategies. In obese patients with type 2 diabetes, visceral adipocytes exposed to chronic/intermittent hyperglycemia develop a new microRNAs' (miRNAs') expression pattern. Visceral preadipocytes memorize the effect of hyperglycemia via changes in miRNAs' expression profile and contribute to the progression of diabetic phenotype. Nonsteroidal anti-inflammatory drugs, metformin, and statins can be beneficial in treating the local or systemic consequences of white adipose tissue inflammation. Rapamycin inhibits leptin-induced LD formation. Collectively, in this chapter, the concept of adipose tissue remodeling in response to adipocyte death or adipogenesis, and the complexity of LD interactions with the other cellular organelles are reviewed. Furthermore, clinical perspective of fat cell turnover in obesity is also debated.

To assess the applicability of the association between estimated glucose disposal rate (eGDR) and all-cause mortality in the elderly population, and the mediating role of brachial-ankle pulse wave velocity (baPWV).

This was a follow-up cohort study based on the cross-sectional survey of community-dwelling elderly. All participants in the study were included between September 2009 and June 2010, and the follow-up time was December 2020. Participants included 1862 Chinese community-dwelling elderly aged 60 years and above. Insulin resistance assessed by eGDR and arterial stiffness assessed by baPWV were the primary exposures of interest. Mortality, which was followed up until December 2020, was the primary outcome. Cox proportional hazards regression models were used to estimate the association of eGDR with mortality. The mediating effect of baPWV in this association was assessed by mediation analysis.

A total of 1826 participants with a mean age of 71.03 years old were included in the study. During the median follow-up of 10.75 years, 334 participants died. The adjusted HR comparing the highest versus the lowest eGDR quartile was 0.22 (95% CI 0.09 to 0.54; p<0.001) in the Cox proportional hazards model. The results of mediation analysis showed that baPWV had a significant mediation impact on the link between eGDR and all-cause mortality both as continuous or categorical variables.

eGDR is an independent predictor of all-cause mortality in the elderly population. baPWV partially mediated the association of eGDR and long-term all-cause mortality as a mediator factor.