Futile cycle of β-oxidation and de novo lipogenesis are associated with essential fatty acids depletion in lipoatrophy

Chaves‐Filho, Adriano B.; Peixoto, Álbert Souza; Castro, Érique; Oliveira, Tiago E.; Perandini, Luiz Augusto; Moreira, Roger William Fernandes; Silva, Railmara P da; Silva, Beatriz P da; Moretti, Eduardo Hermógenes; Steiner, Alexandre A.; Miyamoto, Sayuri; Yoshinaga, Marcos Y.; Festuccia, William

doi:10.1016/j.bbalip.2022.159264

Cited by 3 publications

(3 citation statements)

References 68 publications

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“…This is an important metabolic reaction, which is the first step in the tricarboxylic acid cycle. CS is involved in energy metabolism, lipid metabolism, glucose metabolism and other important physiological processes in the human body 47 , 48 . CS is involved in glucose and lipid metabolism, and is closely associated with exercise-related diseases, diabetes, and other metabolic disorders 49 , 50 .…”

Section: Discussionmentioning

confidence: 99%

MiR-122-5p regulates erastin-induced ferroptosis via CS in nasopharyngeal carcinoma

Guo,

Wang,

et al. 2024

Sci Rep

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Nasopharyngeal carcinoma (NPC) is a tumor that occurs in the nasopharynx. Although advances in detection and treatment have improved the prognosis of NPC the treatment of advanced NPC remains challenging. Here, we explored the effect of microRNA (miR)-122-5p on erastin-induced ferroptosis in NPC cells and the role of ferroptosis in the development of NPC. The effect of miR-122-5p silencing and overexpression and the effect of citrate synthase on erastin-induced lipid peroxidation in NPC cells was analyzed by measuring the amounts of malondialdehyde, Fe2+, glutathione, and reactive oxygen species and the morphological alterations of mitochondria. The malignant biological behavior of NPC cells was examined by cell counting kit-8, EDU, colony formation, Transwell, and wound healing assays. The effects of miR-122-5p on cell proliferation and migration associated with ferroptosis were examined in vivo in a mouse model of NPC generated by subcutaneous injection of NPC cells. We found that erastin induced ferroptosis in NPC cells. miR-122-5p overexpression inhibited CS, thereby promoting erastin-induced ferroptosis in NPC cells and decreasing NPC cell proliferation, migration, and invasion.

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Section: Discussionmentioning

confidence: 99%

MiR-122-5p regulates erastin-induced ferroptosis via CS in nasopharyngeal carcinoma

Guo,

Wang,

et al. 2024

Sci Rep

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“…In any case, the thermogenic mechanisms are essentially adaptive [782,785,786], but their regulation is multifactorial and not completely understood. It is assumed that thermogenesis is carried out by a number of tissues with high metabolic activity, i.e., by incorporating, in part, the residual metabolic energy loss of futile cycling of exergonic combined reac-tions [787,788], or simply shivering [789,790], ineffective processes in liver [791,792] and skeletal muscle [793,794], and, especially, the uncoupling of oxidative phosphorylation in the mitochondria of, mainly, brown adipocytes [795,796]. These are a specific type of cell found in WAT masses and/or in isolated depots around core organs [775,776,780] or vessels needing special protection against the cold and hypothermia [797].…”

Section: The Adipose Organ An Energy-handling Specialization Of the Ctmentioning

confidence: 99%

The Metabolic Syndrome, a Human Disease

Alemany

2024

IJMS

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This review focuses on the question of metabolic syndrome (MS) being a complex, but essentially monophyletic, galaxy of associated diseases/disorders, or just a syndrome of related but rather independent pathologies. The human nature of MS (its exceptionality in Nature and its close interdependence with human action and evolution) is presented and discussed. The text also describes the close interdependence of its components, with special emphasis on the description of their interrelations (including their syndromic development and recruitment), as well as their consequences upon energy handling and partition. The main theories on MS’s origin and development are presented in relation to hepatic steatosis, type 2 diabetes, and obesity, but encompass most of the MS components described so far. The differential effects of sex and its biological consequences are considered under the light of human social needs and evolution, which are also directly related to MS epidemiology, severity, and relations with senescence. The triggering and maintenance factors of MS are discussed, with especial emphasis on inflammation, a complex process affecting different levels of organization and which is a critical element for MS development. Inflammation is also related to the operation of connective tissue (including the adipose organ) and the widely studied and acknowledged influence of diet. The role of diet composition, including the transcendence of the anaplerotic maintenance of the Krebs cycle from dietary amino acid supply (and its timing), is developed in the context of testosterone and β-estradiol control of the insulin-glycaemia hepatic core system of carbohydrate-triacylglycerol energy handling. The high probability of MS acting as a unique complex biological control system (essentially monophyletic) is presented, together with additional perspectives/considerations on the treatment of this ‘very’ human disease.

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“…Lipids were extracted from serum using a method outlined by Draijer et al [29] and from adipose tissue following the procedure described by Chaves-Filho et al [30]. The extracted lipids were then dissolved in a solvent mixture containing acetonitrile, isopropanol, chloroform, and water in a ratio of 35:35:20:10 (v/v/v/v).…”

Section: Serum and Adipose Tissue Untargeted Lipidome Analysismentioning

confidence: 99%

Multi-Omics Reveals Disrupted Immunometabolic Homeostasis and Oxidative Stress in Adipose Tissue of Dairy Cows with Subclinical Ketosis: A Sphingolipid-Centric Perspective

Zhao,

Li,

Tan

et al. 2024

Antioxidants

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Ketosis, especially its subclinical form, is frequently observed in high-yielding dairy cows and is linked to various diseases during the transition period. Although adipose tissue plays a significant role in the development of metabolic disorders, its exact impact on the emergence of subclinical ketosis (SCK) is still poorly understood. The objectives of this study were to characterize and compare the profiling of transcriptome and lipidome of blood and adipose tissue between SCK and healthy cows and investigate the potential correlation between metabolic disorders and lipid metabolism. We obtained blood and adipose tissue samples from healthy cows (CON, n = 8, β-hydroxybutyric acid concentration < 1.2 mmol/L) and subclinical ketotic cows (SCK, n = 8, β-hydroxybutyric acid concentration = 1.2–3.0 mmol/L) for analyzing biochemical parameters, transcriptome, and lipidome. We found that serum levels of nonesterified fatty acids, malonaldehyde, serum amyloid A protein, IL-1β, and IL-6 were higher in SCK cows than in CON cows. Levels of adiponectin and total antioxidant capacity were higher in serum and adipose tissue from SCK cows than in CON cows. The top enriched pathways in whole blood and adipose tissue were associated with immune and inflammatory responses and sphingolipid metabolism, respectively. The accumulation of ceramide and sphingomyelin in adipose tissue was paralleled by an increase in genes related to ceramide biosynthesis, lipolysis, and inflammation and a decrease in genes related to ceramide catabolism, lipogenesis, adiponectin production, and antioxidant enzyme systems. Increased ceramide concentrations in blood and adipose tissue correlated with reduced insulin sensitivity. The current results indicate that the lipid profile of blood and adipose tissue is altered with SCK and that certain ceramide species correlate with metabolic health. Our research suggests that disruptions in ceramide metabolism could be crucial in the progression of SCK, exacerbating conditions such as insulin resistance, increased lipolysis, inflammation, and oxidative stress, providing a potential biomarker of SCK and a novel target for nutritional manipulation and pharmacological therapy.

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Futile cycle of β-oxidation and de novo lipogenesis are associated with essential fatty acids depletion in lipoatrophy

Cited by 3 publications

References 68 publications

MiR-122-5p regulates erastin-induced ferroptosis via CS in nasopharyngeal carcinoma

MiR-122-5p regulates erastin-induced ferroptosis via CS in nasopharyngeal carcinoma

The Metabolic Syndrome, a Human Disease

Multi-Omics Reveals Disrupted Immunometabolic Homeostasis and Oxidative Stress in Adipose Tissue of Dairy Cows with Subclinical Ketosis: A Sphingolipid-Centric Perspective

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