MHO or MUO? White adipose tissue remodeling

Obesity Reviews, Journal Year: 2024, Volume and Issue: 25(4)

Published: Jan. 7, 2024

In this review, we delve into the intricate relationship between white adipose tissue (WAT) remodeling and metabolic aspects in obesity, with a specific focus on individuals metabolically healthy obesity (MHO) unhealthy (MUO). WAT is highly heterogeneous, plastic, dynamically secreting endocrine immune organ. plays crucial role health, involving expansion mode, microenvironment, phenotype, distribution. MHO, beneficial, reducing ectopic fat deposition insulin resistance (IR) through mechanisms like increased adipocyte hyperplasia, anti-inflammatory appropriate extracellular matrix (ECM) remodeling, vascularization, enhanced browning, subcutaneous (SWAT) deposition. Conversely, for those MUO, leads to IR, causing dysregulation. This process involves hypertrophy, disrupted heightened pro-inflammatory brown (BAT) whitening, accumulation of visceral (VWAT) The review underscores pivotal importance intervening hinder transition from MHO MUO. insight valuable tailoring personalized effective management strategies patients clinical practice.

Language: Английский

---

Mammalian IRE1α dynamically and functionally coalesces with stress granules

Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(6), P. 917 - 931

Published: May 7, 2024

Language: Английский

---

Endoplasmic reticulum stress in diseases

MedComm, Journal Year: 2024, Volume and Issue: 5(9)

Published: Aug. 26, 2024

The endoplasmic reticulum (ER) is a key organelle in eukaryotic cells, responsible for wide range of vital functions, including the modification, folding, and trafficking proteins, as well biosynthesis lipids maintenance intracellular calcium homeostasis. A variety factors can disrupt function ER, leading to aggregation unfolded misfolded proteins within its confines induction ER stress. conserved cascade signaling events known protein response (UPR) has evolved relieve burden restore However, these processes culminate cell death while stress sustained over an extended period at elevated levels. This review summarizes potential role UPR determining fate various diseases, cardiovascular neurodegenerative metabolic autoimmune fibrotic viral infections, cancer. It also puts forward that manipulation this intricate pathway may represent novel target drug discovery innovative therapeutic strategies context human diseases.

Language: Английский

---

Insights by which TUDCA is a potential therapy against adiposity

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 21, 2023

Adipose tissue is an organ with metabolic and endocrine activity. White, brown ectopic adipose tissues have different structure, location, function. regulates energy homeostasis, providing in nutrient-deficient conditions storing it high-supply conditions. To attend to the high demand for storage during obesity, undergoes morphological, functional molecular changes. Endoplasmic reticulum (ER) stress has been evidenced as a hallmark of disorders. In this sense, ER inhibitor tauroursodeoxycholic acid (TUDCA), bile conjugated taurine chemical chaperone activity, emerged therapeutic strategy minimize dysfunction alterations associated obesity. review, we highlight effects TUDCA receptors TGR5 FXR on setting demonstrated limit disturbs obesity by inhibiting stress, inflammation, apoptosis adipocytes. The beneficial effect perivascular (PVAT) function adiponectin release may be related cardiovascular protection although more studies are needed clarify mechanisms. Therefore, potential comorbidities.

Language: Английский

---

Rna M⁶a Methylation Regulates Glycolysis of Beige Fat and Contributes to Systemic Metabolic Homeostasis

Advanced Science, Journal Year: 2023, Volume and Issue: 10(25)

Published: July 5, 2023

Abstract N6‐methyladenosine (m 6 A) modification has been implicated in the progression of obesity and metabolic diseases. However, its impact on beige fat biology is not well understood. Here, via m A‐sequencing RNA‐sequencing, this work reports that upon adipocytes activation, glycolytic genes undergo major events A transcriptional activation. Genetic ablation writer Mettl3 tissues reveals deficiency mature leads to suppressed capability thermogenesis, as reduced preadipocytes proliferation product lactate. In addition, specific modulation AAV delivery demonstrates consistently Mettl3's role glucose metabolism, hyperplasia. Mechanistically, reader Igf2bp2 control mRNA stability key adipocytes. Overall, these findings highlight significance systemic energy homeostasis.

Language: Английский

---

Plasticity of Adipose Tissues: Interconversion among White, Brown, and Beige Fat and Its Role in Energy Homeostasis

Biomolecules, Journal Year: 2024, Volume and Issue: 14(4), P. 483 - 483

Published: April 16, 2024

Obesity, characterized by the excessive accumulation of adipose tissue, has emerged as a major public health concern worldwide. To develop effective strategies for treating obesity, it is essential to comprehend biological properties different tissue types and their respective roles in maintaining energy balance. Adipose serves crucial organ storage metabolism human body, with functions extending beyond simple fat encompass regulation homeostasis secretion endocrine factors. This review provides an overview key characteristics, functional differences, interconversion processes among white (WAT), brown (BAT), beige tissue. Moreover, delves into molecular mechanisms recent research advancements concerning browning WAT, activation BAT, whitening BAT. Although targeting holds promise potential approach obesity treatment, further investigations are necessary unravel intricate features various elucidate pathways governing interconversion. Such endeavors will pave way development more efficient targeted therapeutic interventions fight against obesity.

Language: Английский

---

Adipocyte-derived ferroptotic signaling mitigates obesity

Cell Metabolism, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Ferroptosis is characterized as an iron-dependent and lipophilic form of cell death. However, it remains unclear what role ferroptosis has in adipose tissue function activity. Here, we find a lower ferroptotic signature the individuals mice with obesity. We further that activation signaling by non-lethal dose agonists significantly reduces lipid accumulation primary adipocytes high-fat diet (HFD)-fed mice. Notably, adipocyte-specific overexpression acyl-coenzyme A synthetase long-chain family member 4 (Acsl4) or deletion ferritin heavy chain (Fth) protects from HFD-induced expansion metabolic disorders via signaling. Mechanistically, 5,15-dihydroxyeicosatetraenoic acid (5,15-DiHETE) activates signaling, resulting degradation hypoxia-inducible factor-1α (HIF1α), thereby derepressing thermogenic program regulated c-Myc-peroxisome proliferator-activated receptor gamma coactivator-1 beta (Pgc1β) pathway. Our findings suggest activating tissues might help to prevent treat obesity its related disorders.

Language: Английский

---

PRMT4 Facilitates White Adipose Tissue Browning and Thermogenesis by Methylating PPARγ

Diabetes, Journal Year: 2023, Volume and Issue: 72(8), P. 1095 - 1111

Published: May 22, 2023

Obesity is a global health threat, and the induction of white adipose tissue (WAT) browning presents promising therapeutic method for it. Recent publications revealed essential role protein arginine methyltransferase 4 (PRMT4) in lipid metabolism adipogenesis, but its involvement WAT has not been investigated. Our initial studies found that expression PRMT4 adipocytes was upregulated cold-induced downregulated obesity. Besides, overexpression inguinal accelerated thermogenesis to protect against high-fat diet–induced obesity metabolic disruptions. Mechanistically, our work demonstrated methylated peroxisome proliferator-activated receptor-γ (PPARγ) on Arg240 enhance interaction with coactivator PR domain-containing 16 (PRDM16), leading increased thermogenic genes. Taken together, results uncover PRMT4/PPARγ/PRDM16 axis pathogenesis browning. Article Highlights Protein during cold exposure negatively correlated body mass mice humans. improved associated impairment due enhanced heat production. facilitated binding initiate thermogenesis. PRMT4-dependent methylation important process

Language: Английский

---

Impaired RelA signaling and lipid metabolism dysregulation in hepatocytes: driving forces in the progression of metabolic dysfunction-associated steatotic liver disease

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: Feb. 5, 2025

Abstract RelA, also known as nuclear factor kappa B p65, plays a crucial role in the pathogenesis of various liver diseases. However, specific RelA hepatocytes during progression metabolic dysfunction-associated steatotic disease (MASLD) is not well understood. This study explored relationship between impaired signaling and lipid metabolism disorders hepatocytes, how they synergistically contribute to advancement MASLD. We assessed changes, regulatory relationships, impacts remodeling on both vitro vivo. During MASLD, there was decrease expression hepatocyte 1 alpha (HNF1α), with factors showing mutual enhancement each other’s under normal conditions. synergistic effect absent steatosis. or HNF1α depletion intensified MASLD symptoms, whereas overexpression RELA treatment necrostatin-1 (a necroptosis inhibitor) Z-VAD caspase significantly mitigated these effects. Mechanistically, hepatic steatosis, altered profiles exhibited lipotoxicity, inducing apoptosis necroptosis, endoplasmic reticulum (ER) stress triggered processes similar those observed upregulated activating transcription 4 glucose-regulated protein 78, thereby alleviating ER stress. Impaired remodeled response metabolism, enhanced accumulation toxicity. In conclusion, disrupted form detrimental feedback loop that promotes progression. Lipid suppresses signaling, exacerbating disorder, ultimately leading necroptosis.

Language: Английский

---

Targeting IRE1α improves insulin sensitivity and thermogenesis and suppresses metabolically active adipose tissue macrophages in obesity

Published: Feb. 6, 2025

Overnutrition engenders the expansion of adipose tissue and accumulation immune cells, in particular, macrophages, tissue, leading to chronic low-grade inflammation insulin resistance. In obesity, several proinflammatory subpopulations macrophages (ATMs) identified hitherto include conventional “M1-like” CD11C-expressing ATM newly discovered metabolically activated CD9-expressing ATM; however, relationship among is unclear. The ER stress sensor inositol-requiring enzyme 1α (IRE1α) adipocytes cells under obesity. It unknown whether targeting IRE1α capable reversing resistance obesity modulating ATMs. We report that pharmacological inhibition RNase significantly ameliorates glucose intolerance male mice with diet-induced also increases thermogenesis energy expenditure, hence protects against high fat Our study shows CD11c + ATMs are largely overlapping but yet non-identical CD9 obese white tissue. Notably, diminishes obesity-induced ATMs, resulting curtailment ensuing reactivation thermogenesis, without augmentation alternatively M2 macrophage population. findings suggest potential for therapeutic treatment

Language: Английский

---