Acetyl-CoA synthesis in the skin is a key determinant of systemic lipid homeostasis

Cell Reports, Journal Year: 2025, Volume and Issue: 44(2), P. 115284 - 115284

Published: Feb. 1, 2025

ATP-citrate lyase (ACLY) generates cytosolic acetyl-coenzyme A (acetyl-CoA) for lipid synthesis and is a promising therapeutic target in diseases with altered metabolism. Here, we developed inducible whole-body Acly-knockout mice to determine the requirement ACLY normal tissue functions, uncovering its crucial role skin homeostasis. ACLY-deficient upregulates acetyl-CoA synthetase ACSS2; deletion of both Acly Acss2 from exacerbates abnormalities, differential effects on two major lipid-producing compartments. While epidermis depleted barrier lipids, sebaceous glands increase production sebum, supplied at least part by circulating fatty acids coinciding adipose lipolysis fat depletion. Dietary supplementation further boosts sebum partially rescues lipoatrophy aberrant phenotypes. The data establish critical maintaining integrity highlight as key organ systemic regulation.

Language: Английский

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Hepatotoxicity in Carp (Carassius auratus) Exposed to Perfluorooctane Sulfonate (PFOS): Integrative Histopathology and Transcriptomics Analysis

Animals, Journal Year: 2025, Volume and Issue: 15(4), P. 610 - 610

Published: Feb. 19, 2025

Perfluorooctane sulfonate (PFOS) contamination poses a significant environmental threat due to its widespread distribution and persistence. However, the hepatotoxic effects of PFOS on key aquatic species, such as crucian carp, remain understudied. This study systematically investigated hepatotoxicity underlying molecular mechanisms associated with exposure in carp over 21 day period. We determined 96 h 50% lethal concentration (LC50) 23.17 mg/L. Histopathological transcriptomic analyses confirmed PFOS-induced liver damage characterized by venous congestion, nucleolar dissolution cellular vacuolation. Transcriptomic profiling further identified 1036 differentially expressed genes (DEGs), involving critical pathways related lipid energy metabolism, immunity, endocrine regulation. These are integral development nonalcoholic fatty disease (NAFLD). Specifically, DEGs metabolism showed changes, while those involved indicated disrupted ATP production mitochondrial function. Genes immune response revealed an upregulation pro-inflammatory markers, hormone regulation highlighted alterations signaling. Our findings emphasized that exhibits acute toxicity potentially inducing disrupting multiple physiological systems. research provides theoretical foundation for mitigating pollution protecting eco-health, contributing broader ecological conservation biology discussions.

Language: Английский

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Adipokines as Cardioprotective Factors: BAT Steps Up to the Plate

Biomedicines, Journal Year: 2025, Volume and Issue: 13(3), P. 710 - 710

Published: March 13, 2025

Cardiovascular disease is the leading cause of death throughout most industrialized world. Metabolic syndrome (MetS) and its associated pathologies are underlying factors in etiology cardiovascular disease, as well a plethora other maladies which excess morbidity mortality. Adipose tissue (AT) has come to be regarded bona fide endocrine organ secretes specific molecular entities constituting part complex web inter-organ crosstalk that functions key determinant whole-body metabolic phenotype. Brown adipose (BAT) classically been thermogenic exerting effects primarily through capacity oxidize substrates decoupled from ATP resynthesis, thereby resulting increased energy expenditure (EE) heat production. However, recent years, BAT begun receive attention secretory own right. The molecules secreted specifically by have termed “batokines”, currently available evidence supports notion batokines exert favorable on multiple systems. While maintenance healthy body composition conferring resistance excessive adiposity rather obvious mechanism operates via EE, critical organs such heart remain unclear. This narrative review focuses four types (FGF21, neuregulin 4, 12,13-diHOME, BAT-derived microRNAs) for modulation function exists context pathological states hypertension, atherosclerosis, ischemia/reperfusion injury. Given overwhelming burden cardiometabolic further study secretome warranted will intensify future.

Language: Английский

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PPARα regulates ER–lipid droplet protein Calsyntenin-3β to promote ketogenesis in hepatocytes

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(17)

Published: April 21, 2025

Ketogenesis requires fatty acid flux from intracellular (lipid droplets) and extrahepatic (adipose tissue) lipid stores to hepatocyte mitochondria. However, whether interorganelle contact sites regulate this process is unknown. Recent studies have revealed a role for Calsyntenin-3β (CLSTN3β), an endoplasmic reticulum–lipid droplet site protein, in the control of utilization adipose tissue. Here, we show that Clstn3b expression induced liver by nuclear receptor PPARα settings high utilization, including fasting ketogenic diet feeding. Hepatocyte-specific loss CLSTN3β mice impairs ketogenesis independent changes activation. Conversely, hepatic overexpression promotes mice. Mechanistically, affects LD–mitochondria crosstalk, as evidenced oxidation, lipid-dependent mitochondrial respiration, integrated stress response. These findings define function CLSTN3β-dependent membrane contacts ketogenesis.

Language: Английский

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