Biology subjects

de Freitas, H. S.

Publications and source records attributed to de Freitas, H. S..

2 recordsLinked to original sources

bioRxiv2026

Severely lipoatrophic mice are hypermetabolic and hyperthermic under thermoneutral conditions in part due to an enhanced liver de novo lipogenesis

White, beige and brown adipocytes store energy as lipids, secrete hormones and produce heat, playing an important role in the regulation of energy balance through not completely defined mechanisms. We investigate herein the impact of the almost complete absence of mature adipocytes (severe lipoatrophy) in the determination of energy balance (energy intake and expenditure) and homeothermy in mice. For this, mice with severe lipoatrophy induced by adipocyte deletion of peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) (PPAR{gamma} flox adiponectin-Cre) and littermate controls (PPAR{gamma} flox) were evaluated for energy balance, thermoneutral zone, core body temperature, locomotor activity, and gene expression profiles at different ambient temperatures. Severely lipoatrophic mice are heavier, hypermetabolic and hyperphagic and feature a widened thermoneutral zone, lower ambulatory activity, and metabolic inflexibility at both 23 and 17{degrees}C, along with unstable thermal behavior characterized by hyperthermia at 30{degrees}C, normothermia at 23{degrees}C, and bouts of hypothermia at 17{degrees}C. Noteworthy, lipoatrophic mice hypermetabolism at 30{degrees}C is not due to thyroid hormones, impaired insulation or increased body and lean masses and is not altered by pharmacological blockade of either {beta}-adrenergic receptor signaling with propranolol or skeletal muscle sarcoplasmic/endoplasmic reticulum Ca2+-ATPases (SERCA) and sarcolipin (SLN)-mediated calcium cycling with dantrolene, but is partially attenuated by pharmacological inhibition of acetyl-CoA carboxylase (ACC) and de novo lipogenesis with ND-630. In conclusion, severe lipoatrophy causes hypermetabolism and hyperthermia at 30{degrees}C partly through the activation of liver de novo fatty acid synthesis.

physiology↗

bioRxiv2026

Hepatocyte-, but not myeloid cell-Rictor/mTORC2 deficiency moderately attenuates steatotic liver disease induced by intake of a choline-deficient, amino acid-defined high-fat diet

Previous studies have demonstrated that mechanistic target of rapamycin complex 2 (mTORC2) deficiency provides complete protection against steatotic liver disease driven by constitutive activation of the phosphoinositide 3-kinase (PI3K)-Akt signaling pathway and de novo lipogenesis, and partial protection against disease induced by a high-fat diet. We investigated herein whether mTORC2 deficiency in hepatocytes and myeloid cells, including Kupffer cells and recruited macrophages, influences the development of liver disease induced by intake of a choline-deficient, amino acid-defined high-fat diet (CDAHFD), a model in which liver disease is induced by impaired hepatic secretion of very low-density lipoprotein (VLDL) triacylglycerol. For this, mice with either hepatocyte- or myeloid cells-specific deletion of mTORC2 essential component rapamycin-insensitive companion of mTOR (Rictor) and their respective littermate controls were fed with either chow or CDAHFD for 10 weeks and evaluated for hepatic steatosis, inflammation and fibrosis. Our main findings indicate that hepatocyte Rictor/mTORC2 deficiency slightly attenuated the CDAHFD-induced increases in liver mass, macrovesicular steatosis and triacylglycerol accumulation, without affecting though liver cholesterol, serum markers of liver injury (AST and ALT), as well as the upregulation in proinflammatory cytokine IL-1{beta} and expression of fibrosis-related genes. Myeloid cells-Rictor deletion had no detectable impact on liver steatosis, inflammatory, or fibrosis induced by CDAHFD. In conclusion, mTORC2 deficiency show modest beneficial effects in counteracting liver disease induced by CDAHFD intake.

biochemistry↗