An Integrated View of Immunometabolism

Cell, Год журнала: 2018, Номер 172(1-2), С. 22 - 40

Опубликована: Янв. 1, 2018

The worldwide obesity epidemic has emerged as a major cause of insulin resistance and Type 2 diabetes. Chronic tissue inflammation is well-recognized feature obesity, the field immunometabolism witnessed many advances in recent years. Here, we review features our current understanding with respect to chronic obesity-related metabolic tissues focus on how these inflammatory changes affect sensitivity, secretion, food intake, glucose homeostasis. There growing appreciation varied sometimes integrated crosstalk between cells within (intraorgan) an organism (interorgan) that supports context dysregulation. Understanding pathways modes communication implications for translational studies. We also briefly summarize state this potential developing therapeutics.

Язык: Английский

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The Role of the Pentose Phosphate Pathway in Diabetes and Cancer

Frontiers in Endocrinology, Год журнала: 2020, Номер 11

Опубликована: Июнь 9, 2020

The pentose phosphate pathway (PPP) branches from glucose 6-phosphate (G6P), produces NADPH and ribose 5-phosphate (R5P), shunts carbons back to the glycolytic or gluconeogenic pathway. PPP has been demonstrated be a major regulator for cellular reduction-oxidation (redox) homeostasis biosynthesis. Enzymes in are reported play important roles many human diseases. In this review, we will discuss role of type 2 diabetes cancer.

Язык: Английский

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Metabolic adaptation and maladaptation in adipose tissue

Nature Metabolism, Год журнала: 2019, Номер 1(2), С. 189 - 200

Опубликована: Янв. 9, 2019

Язык: Английский

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Thirty sweet years of GLUT4

Journal of Biological Chemistry, Год журнала: 2019, Номер 294(30), С. 11369 - 11381

Опубликована: Июнь 8, 2019

A pivotal metabolic function of insulin is the stimulation glucose uptake into muscle and adipose tissues. The discovery insulin-responsive transporter type 4 (GLUT4) protein in 1988 inspired its molecular cloning following year. It also spurred numerous cellular mechanistic studies laying foundations for how regulates by fat cells. Here, we reflect on importance GLUT4 chronicle additional key findings made past 30 years. That exocytosis a multispanning membrane transport illuminated novel adaptation secretory pathway, which to transiently modulate composition plasma membrane. controls tissues response during exercise. Thus, investigation regulated trafficking provides major means map essential signaling components that transmit effects Manipulation expression or GLUT4-regulating molecules mice has revealed impact whole-body metabolism. Remaining gaps our understanding regulation are highlighted here, along with opportunities future discoveries development therapeutic approaches manage disease.

Язык: Английский

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Thiazolidinediones: the Forgotten Diabetes Medications

Current Diabetes Reports, Год журнала: 2019, Номер 19(12)

Опубликована: Ноя. 27, 2019

Abstract Purpose of Review Thiazolidinediones (TZDs) are the only pharmacologic agents that specifically treat insulin resistance. The beneficial effects TZDs on cardiovascular risk factors associated with resistance have been well documented. TZD use has limited because concern about safety issues and side effects. Recent Findings studies indicate toxicity rosiglitazone increase in bladder cancer pioglitazone no longer significant issues. There new data which show treatment reduces myocardial infarctions ischemic strokes. New concerning TZD-mediated edema, congestive heart failure, bone fractures improves clinician’s ability to select patients will minimal Summary now generic less costly than pharmaceutical company–promoted therapies. Better understanding coupled clear benefits components syndrome should promote treating type 2 diabetes.

Язык: Английский

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A new immunometabolic perspective of intervertebral disc degeneration

Nature Reviews Rheumatology, Год журнала: 2021, Номер 18(1), С. 47 - 60

Опубликована: Ноя. 29, 2021

Язык: Английский

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Obesity cardiomyopathy: evidence, mechanisms, and therapeutic implications

Physiological Reviews, Год журнала: 2021, Номер 101(4), С. 1745 - 1807

Опубликована: Май 5, 2021

The prevalence of heart failure is on the rise and imposes a major health threat, in part, due to rapidly increased overweight obesity. To this point, epidemiological, clinical, experimental evidence supports existence unique disease entity termed "obesity cardiomyopathy," which develops independent hypertension, coronary disease, other diseases. Our contemporary review evaluates for pathological condition, examines putative responsible mechanisms, discusses therapeutic options disorder. Clinical findings have consolidated presence left ventricular dysfunction Experimental investigations uncovered pathophysiological changes myocardial structure function genetically predisposed diet-induced Indeed, consolidates wide array cellular molecular mechanisms underlying etiology obesity cardiomyopathy including adipose tissue dysfunction, systemic inflammation, metabolic disturbances (insulin resistance, abnormal glucose transport, spillover free fatty acids, lipotoxicity, amino acid derangement), altered intracellular especially mitochondrial Ca2+ homeostasis, oxidative stress, autophagy/mitophagy defect, fibrosis, dampened flow reserve, microvascular (microangiopathy), endothelial impairment. Given important role risk failure, that with preserved systolic recent rises COVID-19-associated cardiovascular mortality, should provide compelling cardiomyopathy, various comorbid conditions, offer new insights into potential approaches (pharmacological lifestyle modification) clinical management cardiomyopathy.

Язык: Английский

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Diagnosis of obesity and use of obesity biomarkers in science and clinical medicine

Metabolism, Год журнала: 2018, Номер 92, С. 61 - 70

Опубликована: Дек. 23, 2018

Язык: Английский

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Insulin resistance and insulin hypersecretion in the metabolic syndrome and type 2 diabetes: Time for a conceptual framework shift

Diabetes and Vascular Disease Research, Год журнала: 2019, Номер 16(2), С. 118 - 127

Опубликована: Фев. 15, 2019

While few dispute the existence of metabolic syndrome as a clustering factors indicative poor health, its utility above that individual components in clinical care patients is questioned. This likely consequence failure clinicians and scientists to agree on unifying mechanism explain syndrome. Insulin resistance has most commonly been proposed for this role generally considered be root causative factor not only but also associated conditions non-alcoholic fatty liver disease (NAFLD), polycystic ovary (PCOS), obesity-related type 2 diabetes (T2D) atherosclerotic cardiovascular (ASCVD). An alternative view, which evidence mounting, hyper-responsiveness islet β-cells hostile environment, such westernised lifestyle, primary resulting hyperinsulinaemia drives other Importantly, within new conceptual framework, insulin resistance, while always biomarker state harmful, protective adaptive response critical tissues including myocardium against insulin-induced stress. major shift how can puts hypersecretion into position mechanism. If shown correct, framework implications future prevention management syndrome, NAFLD, PCOS, T2D ASCVD.

Язык: Английский

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Mediterranean Diet Nutrients to Turn the Tide against Insulin Resistance and Related Diseases

Nutrients, Год журнала: 2020, Номер 12(4), С. 1066 - 1066

Опубликована: Апрель 12, 2020

Insulin resistance (IR), defined as an attenuated biological response to circulating insulin, is a fundamental defect in obesity and type 2 diabetes (T2D), also linked wide spectrum of pathological conditions, such non-alcoholic fatty liver disease (NAFLD), cognitive impairment, endothelial dysfunction, chronic kidney (CKD), polycystic ovary syndrome (PCOS), some endocrine tumors, including breast cancer. In obesity, the unbalanced production pro- anti-inflammatory adipocytokines can lead development IR its related metabolic complications, which are potentially reversible through weight-loss programs. The Mediterranean diet (MedDiet), characterized by high consumption extra-virgin olive oil (EVOO), nuts, red wine, vegetables other polyphenol-rich elements, has proved be associated with greater improvement obese individuals, when compared nutritional interventions. Also, recent studies either experimental animal models or humans, have shown encouraging results for insulin-sensitizing supplements derived from MedDiet food sources modulation pathognomonic traits certain IR-related polyunsaturated acids seeds, anthocyanins purple fruits, resveratrol grapes, EVOO-derived, oleacein. Although pharmacological properties clinical uses these functional nutrients still under investigation, molecular mechanism(s) underlying benefits appear compound-specific and, cases, point role gene expression involvement nuclear high-mobility group A1 (HMGA1) protein.

Язык: Английский

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