Metabolism: Clinical and Experimental

BACKGROUND: The monocarboxylate transporter 1 (MCT1) is a member of the MCT family and is implicated in the transport of lactate and a few other monocarboxylates across the cell membrane. How hepatic MCT1 regulates the metabolic functions of the body is currently unknown. METHODS: The functions of hepatic MCT1 on metabolism were analyzed using a mouse model with liver-specific deletion of Slc16a1 that encodes MCT1. Obesity and hepatosteatosis of the mice were induced by high fat diet (HFD)...

BACKGROUND: Exposure to cold temperature stimulates the sympathetic nervous system that activates β-adrenergic receptor signals in brown and beige adipocytes, leading to the induction of adaptive thermogenesis in mammals. Prominin-1 (PROM1) is a pentaspan transmembrane protein that is widely identified as a marker for stem cells, although the role of this protein as a regulator of many intracellular signaling cascades has been recently delineated. The main focus of the current study is to identify the previously unknown role of PROM1 in beige adipogenesis and adaptive thermogenesis...

BACKGROUND: The gut derived anorexigenic hormone neurotensin (NT) is upregulated after bariatric surgery which may contribute to the sustained weight loss. In contrast, diet-induced weight loss is most often followed by weight regain. We therefore investigated whether diet-induced weight loss impacts levels of circulating NT in mice and humans and whether NT levels predicts body weight change after weight loss in humans. METHODS: In vivo mice study: Obese mice were fed ad-libitum or a restricted diet (40-60 % of average food intake) for 9 days to obtain similar weight loss as observed in the human study...

BACKGROUND: Fibroblast growth factor 21 (FGF21) levels are often elevated in heart failure (HF), although this has not been assessed using a longitudinal study design. Therefore, we investigated the association between baseline plasma FGF21 levels and incident HF in the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS: A total of 5408 participants, free of clinically apparent cardiovascular disease, were included in the analysis, of which 342 developed HF over a median follow-up period of 16...

Sarcopenia is a geriatric condition featured by a progressive loss of muscle mass and function and associated with various adverse health outcomes. In this review, we aimed to summarize the epidemiological features of sarcopenia as well as consequences and risk factors of the disease. We performed a systematic review of meta-analysis on sarcopenia to collect data. The prevalence of sarcopenia varied between studies and depending on definition used. Sarcopenia was estimated to influence 10 %-16 % of the elderly worldwide...

Heart diseases are associated with substantial morbidity and mortality worldwide. The underlying mechanisms and pathological changes associated with cardiac diseases are exceptionally complex. Highly active cardiomyocytes require sufficient energy metabolism to maintain their function. Under physiological conditions, the choice of fuel is a delicate process that depends on the whole body and organs to support the normal function of heart tissues. However, disordered cardiac metabolism has been discovered to play a key role in many forms of heart diseases, including ischemic heart disease, cardiac hypertrophy, heart failure, and cardiac injury induced by diabetes or sepsis...

BACKGROUND AND AIMS: Obesity is a state of chronic low-grade systemic inflammation. Recent studies showed that NLRP3 inflammasome initiates metabolic dysregulation in adipose tissues, primarily through activation of adipose tissue infiltrated macrophages. However, the mechanism of NLRP3 activation and its role in adipocytes remains elusive. Therefore, we aimed to examine the activation of TNFα-induced NLRP3 inflammasome in adipocytes and its role on adipocyte metabolism and crosstalk with macrophages...

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Klotho is a critical protein that protects the kidney. Klotho is severely downregulated in chronic kidney disease (CKD), and its deficiency is implicated in the pathogenesis and progression of CKD. Conversely, an increase in Klotho levels results in improved kidney function and delays CKD progression, supporting the notion that modulating Klotho levels could represent a possible therapeutic strategy for CKD treatment. Nevertheless, the regulatory mechanisms responsible for the loss of Klotho remain elusive...

INTRODUCTION: Aging is characterized by progressive metabolic dyshomeostasis that increases morbidity and mortality. Solutions for optimizing healthy aging are challenged by lacking appropriate biomarkers. Moreover, druggable targets to rejuvenate the aging-associated metabolic phenotypes remain unavailable. METHODS: Proteomics analysis was performed in a cohort of young and elderly adults. Circulating levels of insulin-like growth factor 1 (IGF-1) and fatty acid binding protein 4 (FABP4) were evaluated by ELISA...

BACKGROUND: Folate (FA) is an essential cofactor in the one-carbon (1C) metabolic pathway and participates in amino acid metabolism, purine and thymidylate synthesis, and DNA methylation. FA metabolism has been reported to play an important role in viral replications; however, the roles of FA metabolism in the antiviral innate immune response are unclear. OBJECTIVE: To evaluate the potential regulatory role of FA metabolism in antiviral innate immune response, we establish the model of FA deficiency (FAD) in vitro and in vivo...

BACKGROUND: Little is known about the subtypes of type 2 diabetes (T2D) and their association with clinical outcomes in Asians. METHODS: We performed data-driven cluster analysis in patients with newly diagnosed drug-naive T2D (n = 756) from the Korean Genome and Epidemiology Study. Clusters were based on five variables (age at diagnosis, BMI, HbA1c, and HOMA2 β-cell function, and insulin resistance). RESULTS: We identified four clusters of patients with T2D according to k-means clustering: cluster 1 (22...

BACKGROUND AND AIMS: Hyperglucagonemia is a characteristic feature of type 2 diabetes mellitus (T2DM). We examined the effect of chronic (48-72 h) physiologic increase (+50 mg/dl) in plasma glucose concentration on suppression of plasma glucagon concentration by insulin and by hyperglycemia in normal glucose tolerance (NGT) individuals. MATERIALS AND METHODS: Study One: 16 NGT subjects received OGTT and 3-step hyperinsulinemic (10, 20, 40 mU/m2 ·min) euglycemic clamp before and after 48 hour glucose infusion to increase plasma glucose by ~50 mg/dl...

BACKGROUND: Patients with diabetes and obesity are populations at high-risk for severe COVID-19 outcomes and have shown blunted immune responses when administered different vaccines. Here we used the 'ANRS0001S COV-POPART' French nationwide multicenter prospective cohort to investigate early humoral response to COVID-19 vaccination in the sub-cohort ('COVPOP OBEDIAB') of patients with obesity and diabetes. METHODS: Patients with diabetes (n = 390, type 1 or 2) or obesity (n = 357) who had received two vaccine doses and had no history of previous COVID-19 infection and negative anti-nucleocapsid (NCP) antibodies were included and compared against healthy subjects (n = 573)...

BACKGROUND: A significant proportion of premature deaths globally are related to metabolic diseases in young adults. We examined the global trends and mortality of metabolic diseases in individuals aged below 40 years using data from the Global Burden of Diseases, Injuries and Risk Factors Study (GBD) 2019. METHODS: From 2000 to 2019, global estimates of deaths and disability-adjusted life years (DALYs) were described for metabolic diseases (type 2 diabetes mellitus [T2DM], hyperlipidemia, hypertension, obesity, non-alcoholic fatty liver disease [NAFLD])...

BACKGROUND: The trajectory from healthy to critical illness is influenced by numerous factors, including metabolism, which differs substantially between males and females. Whole body protein breakdown is substantially increased in critically ill patients, but it remains unclear whether there are sex differences that could explain the different health outcomes. Hence, we performed a secondary analysis of a study, where we used a novel pulse isotope method in critically ill and matched healthy males and females...

BACKGROUND AND AIMS: In 2019, the EAT-Lancet Commission proposed a mainly plant-based diet that nurtures human health and supports environmental sustainability. However, its association with type 2 diabetes (T2D) has not been widely studied, and it remains unclear whether genetic susceptibility for T2D can modify this association. The aim was therefore to investigate the association between the EAT-Lancet diet and risk of T2D and assess whether the association differs by the genetic predisposition to T2D...

BACKGROUND: Production rates of the short-chain fatty acids (SCFA) acetate, propionate, and butyrate, which are beneficial metabolites of the intestinal microbiota, are difficult to measure in humans due to inaccessibility of the intestine to perform measurements, and the high first-pass metabolism of SCFAs in colonocytes and liver. We developed a stable tracer pulse approach to estimate SCFA whole-body production (WBP) in the accessible pool representing the systemic circulation and interstitial fluid...

INTRODUCTION: Cell therapy with mesenchymal stem cells (MSCs) and biomaterials holds great potential for the treatment of diabetic ulceration; however, the underlying mechanism as well as its compatibility with the first-line anti-diabetic drug, metformin (MTF), has not been well elucidated. METHODS: MSCs derived from the umbilical cord were labeled with fluorescent proteins, followed by transplantation in a fibrin scaffold (MSCs/FG) onto the STZ-induced diabetic wound in a C57BL6/J mouse model...

BACKGROUND: The regulatory mechanisms involved in mitochondrial quality control (MQC) dysfunction during septic cardiomyopathy (SCM) remain incompletely characterized. Transmembrane BAX inhibitor motif containing 6 (TMBIM6) is an endoplasmic reticulum protein with Ca2+ leak activity that modulates cellular responses to various cellular stressors. METHODS: In this study, we evaluated the role of TMBIM6 in SCM using cardiomyocyte-specific TMBIM6 knockout (TMBIM6CKO ) and TMBIM6 transgenic (TMBIM6TG ) mice...