Adipose Signals Regulating Distal Organ Health and Disease

Diabetes, Journal Year: 2024, Volume and Issue: 73(2), P. 169 - 177

Published: Jan. 19, 2024

Excessive adiposity in obesity is a significant risk factor for development of type 2 diabetes (T2D), nonalcoholic fatty liver disease, and other cardiometabolic diseases. An unhealthy expansion adipose tissue (AT) results reduced adipogenesis, increased adipocyte hypertrophy, hypoxia, chronic low-grade inflammation, macrophage infiltration, insulin resistance. This ultimately culminates AT dysfunction characterized by decreased secretion antidiabetic adipokines such as adiponectin adipsin proinflammatory prodiabetic including RBP4 resistin. imbalance adipokine alters the physiological state communication with target organs pancreatic β-cells, heart, liver. In are known to have direct effect on secretion, gene expression, cell death, and/or dedifferentiation. For instance, impaired adipsin, which promotes β-cell identity, failure T2D, thus presenting potential druggable improve preserve function. The cardiac affected both classic white AT–secreted newly recognized brown (BAT)-secreted BATokines or lipokines that alter lipid deposition ventricular liver, affect hepatic gluconeogenesis, accumulation, sensitivity, underscoring importance adipose-liver pathogenesis disease. this perspective, we outline what currently about effects individual heart.

Language: Английский

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AMPK and the Endocrine Control of Metabolism

Endocrine Reviews, Journal Year: 2023, Volume and Issue: 44(5), P. 910 - 933

Published: April 28, 2023

Complex multicellular organisms require a coordinated response from multiple tissues to maintain whole-body homeostasis in the face of energetic stressors such as fasting, cold, and exercise. It is also essential that energy stored efficiently with feeding chronic nutrient surplus occurs obesity. Mammals have adapted several endocrine signals regulate metabolism changes availability demand. These include hormones altered by fasting refeeding including insulin, glucagon, glucagon-like peptide-1, catecholamines, ghrelin, fibroblast growth factor 21; adipokines leptin adiponectin; cell stress-induced cytokines like tumor necrosis alpha differentiating 15, lastly exerkines interleukin-6 irisin. Over last 2 decades, it has become apparent many these factors control regulating activity AMPK (adenosine monophosphate-activated protein kinase). master regulator homeostasis, phosphorylating over 100 distinct substrates are critical for controlling autophagy, carbohydrate, fatty acid, cholesterol, metabolism. In this review, we discuss how integrates balance diverse homeostatic challenges. We present some considerations respect experimental design which should enhance reproducibility fidelity conclusions.

Language: Английский

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Neuregulin 4 as a novel adipokine in energy metabolism

Frontiers in Physiology, Journal Year: 2023, Volume and Issue: 13

Published: Jan. 10, 2023

Adipose tissue has been shown to play a key role in energy metabolism and it regulate metabolic homeostasis through the secretion of adipokines. Neuregulin 4 (Nrg4), novel adipokine secreted mainly by brown adipose (BAT), recently characterized as having an important effect on regulation glucolipid metabolism. Nrg4 can modulate BAT-related thermogenesis increasing sympathetic innervation therefore potential benefits. improves dysregulation various diseases such insulin resistance, obesity, non-alcoholic fatty liver disease, diabetes several mechanisms anti-inflammation, autophagy regulation, pro-angiogenesis, lipid normalization. However, inconsistent findings are found regarding effects clinical settings, this heterogeneity needs be further clarified future studies. The protective suggests that may promising endocrine therapeutic target.

Language: Английский

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Melatonin attenuates diabetic cardiomyopathy by increasing autophagy of cardiomyocytes via regulation of VEGF-B/GRP78/PERK signaling pathway

Cardiovascular Diabetology, Journal Year: 2024, Volume and Issue: 23(1)

Published: Jan. 9, 2024

Abstract Aims Diabetic cardiomyopathy (DCM) is a major cause of mortality in patients with diabetes, and the potential strategies for treating DCM are insufficient. Melatonin (Mel) has been shown to attenuate DCM, however, underlying mechanism remains unclear. The role vascular endothelial growth factor-B (VEGF-B) little known. In present study, we aimed investigate whether Mel alleviated via regulation VEGF-B explored its mechanisms. Methods results We found that significantly cardiac dysfunction improved autophagy cardiomyocytes type 1 diabetes mellitus (T1DM) induced mice. was highly expressed mice comparison normal mice, expression markedly reduced after treatment. treatment diminished interaction Glucose-regulated protein 78 (GRP78) GRP78 kinase RNA -like ER (PERK). Furthermore, increased phosphorylation PERK eIF2α, then up-regulated ATF4. −/− imitated effect on wild diabetic Interestingly, injection Recombinant adeno-associated virus serotype 9 (AAV9)-VEGF-B or administration GSK2656157 (GSK), an inhibitor phosphorylated abolished protective DCM. rapamycin, agonist displayed similar treatment; while 3-Methyladenine (3-MA), neutralized high glucose-treated neonatal rat ventricular myocytes. Conclusions These demonstrated attenuated increasing cardiomyocytes, this cardio-protective dependent VEGF-B/GRP78/PERK signaling pathway.

Language: Английский

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Exercise-induced adipokine Nrg4 alleviates MASLD by disrupting hepatic cGAS-STING signaling

Cell Reports, Journal Year: 2025, Volume and Issue: 44(2), P. 115251 - 115251

Published: Jan. 31, 2025

Language: Английский

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The mTOR Signaling Pathway: Key Regulator and Therapeutic Target for Heart Disease

Biomedicines, Journal Year: 2025, Volume and Issue: 13(2), P. 397 - 397

Published: Feb. 7, 2025

Heart disease, including myocardial infarction, heart failure, cardiac hypertrophy, and cardiomyopathy, remains a leading cause of mortality worldwide. The mammalian target rapamycin (mTOR) is centrally regulated kinase that governs key cellular processes, growth, proliferation, metabolism, survival. Notably, mTOR plays pivotal role in cardiovascular health particularly the onset progression conditions. In this review, we discuss mTOR’s structure function as well regulatory mechanisms its associated signaling pathways. We focus on molecular by which regulates diseases potential inhibitors related drugs preventing these conclude pathway promising therapeutic for disease.

Language: Английский

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Autophagy in High-Fat Diet and Streptozotocin-Induced Metabolic Cardiomyopathy: Mechanisms and Therapeutic Implications

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1668 - 1668

Published: Feb. 15, 2025

Metabolic cardiomyopathy, encompassing diabetic and obese is an escalating global health concern, driven by the rising prevalence of metabolic disorders such as insulin resistance, type 1 2 diabetes, obesity. These conditions induce structural functional alterations in heart, including left ventricular dysfunction, fibrosis, ultimately heart failure, particularly presence coronary artery disease or hypertension. Autophagy, a critical cellular process for maintaining cardiac homeostasis, frequently disrupted cardiomyopathy. This review explores role autophagy pathogenesis high-fat diet (HFD) streptozotocin (STZ)-induced focusing on non-selective selective pathways, mitophagy, ER-phagy, ferritinophagy. Key proteins genes PINK1, Parkin, ULK1, AMPK, mTOR, ATG7, ATG5, Beclin-1, miR-34a are central to regulation Dysregulated autophagic flux impairs mitochondrial function, promotes oxidative stress, drives fibrosis heart. Additionally, processes lipophagy, regulated PNPLA8, ferritinophagy, modulated NCOA4, play pivotal roles lipid metabolism iron homeostasis. Emerging therapeutic strategies targeting autophagy, plant extracts (e.g., curcumin, dihydromyricetin), endogenous compounds sirtuin 3, LC3), lipid/glucose-lowering drugs, offer promising avenues mitigating effects Despite recent advances, precise mechanisms underlying this context remain poorly understood. A deeper understanding autophagy's regulatory networks, involving these proteins, may lead novel approaches treating

Language: Английский

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Targeting mitochondrial quality control for diabetic cardiomyopathy: Therapeutic potential of hypoglycemic drugs

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 168, P. 115669 - 115669

Published: Oct. 10, 2023

Diabetic cardiomyopathy is a chronic cardiovascular complication caused by diabetes that characterized changes in myocardial structure and function, ultimately leading to heart failure even death. Mitochondria serve as the provider of energy cardiomyocytes, mitochondrial dysfunction plays central role development diabetic cardiomyopathy. In response series pathological dysfunction, quality control system activated. The (including biogenesis, fusion fission, mitophagy) core maintaining normal mitochondria performing their physiological functions. However, abnormal cardiomyopathy, resulting insufficient excessive fission within cardiomyocyte, fragmented are not phagocytosed timely manner, accumulating cardiomyocyte injury. Currently, there no specific therapy or prevention for glycemic remains mainstay. this review, we first elucidate pathogenesis explore link between Then, summarize how clinically used hypoglycemic agents sodium-glucose cotransport protein 2 inhibitions, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, thiazolidinediones, metformin, α-glucosidase inhibitors) exert cardioprotective effects treat prevent targeting system. addition, mechanisms complementary alternative therapies, such active ingredients traditional Chinese medicine, exercise, lifestyle, treatment also added, which lays foundation excavation new drugs.

Language: Английский

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The protection of luteolin against diabetic cardiomyopathy in rats is related to reversing JNK-suppressed autophagy

Food & Function, Journal Year: 2023, Volume and Issue: 14(6), P. 2740 - 2749

Published: Jan. 1, 2023

Luteolin improves cardiac function and myocardial remodeling with down-regulation of JNK/c-Jun/miR-221 pathway-inhibited autophagy in the diabetic heart, suggesting that luteolin's inhibition DCM is associated reversing JNK-suppressed autophagy.

Language: Английский

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Targeting autophagy drug discovery: Targets, indications and development trends

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 267, P. 116117 - 116117

Published: Jan. 23, 2024

Language: Английский

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