Metabolism

Sterol O-Acyltransferase Inhibition Ameliorates High-Fat Diet-Induced Renal Fibrosis and Tertiary Lymphoid Tissue Maturation after Ischemic Reperfusion Injury

Metabolic syndrome is associated with the development of chronic kidney disease (CKD). We previously demonstrated that aged kidneys are prone to developing tertiary lymphoid tissues (TLTs) and sustain inflammation after injury, leading to CKD progression; however, the relationship between renal TLT and metabolic syndrome is unknown. In this study, we demonstrated that a high-fat diet (HFD) promoted renal TLT formation and inflammation via sterol O-acyltransferase (SOAT) 1-dependent mechanism.

Peripherally restricted oxytocin is sufficient to reduce food intake and motivation, while CNS-entry is required for locomotor and taste avoidance effects

Oxytocin (OT) has a well-established role in reproductive behaviors, however, it recently emerged as an important regulator of energy homeostasis. In addition to CNS, OT is found in the plasma and oxytocin receptors (OT-R) are found in peripheral tissues relevant to energy balance regulation. Here we aim to determine whether peripheral OT-R activation is sufficient to alter energy intake and expenditure.We first show that systemic OT potently reduced food intake and food-motivated behavior for a high-fat reward in male and female rats.

Keeping brown fat brown

The multilocular phenotype of brown adipose tissue is determined by an ER-lipid droplet anchoring protein.

LepRb cell-specific deletion of Slug mitigates obesity and NAFLD

Leptin exerts its biological actions by activating LepRb. LepRb signaling impairment and leptin resistance are believed to cause obesity. Transcription factor Slug (also known as Snai2) recruits epigenetic modifiers and regulates gene expression by an epigenetic mechanism; however, its epigenetic action has not been explored in leptin resistance. Here, we uncover a pro-obesity function of neuronal Slug. Hypothalamic Slug was upregulated in obese mice.

Dual roles of hexokinase 2 in shaping microglial function by gating glycolytic flux and mitochondrial activity

Microglia continuously survey the brain parenchyma and actively shift status following stimulation. These processes demand a unique bioenergetic programme; however, little is known about the metabolic determinants in microglia. By mining large datasets and generating transgenic tools, here we show that hexokinase 2 (HK2), the most active isozyme associated with mitochondrial membrane, is selectively expressed in microglia in the brain.

HETEROGENEITY IN DIABETES AND BETA CELLS

As well as being a key risk factor for the development of nonalcoholic fatty liver disease (NAFLD), type 2 diabetes (T2D) also appears to accelerate NAFLD progression. Liver biopsy is the reference standard for the diagnosis of the severe form of NAFLD, nonalcoholic steatohepatitis (NASH), and there are two key, non-interchangeable, standardized histologic scoring systems used to evaluate disease features.

Post-fast refeeding enhances intestinal stem cell-mediated regeneration and tumourigenesis through mTORC1-dependent polyamine synthesis

For more than a century, fasting regimens have improved health, lifespan, and tissue regeneration in diverse organisms, including humans. However, how fasting and post-fast refeeding impact adult stem cells and tumour formation has yet to be explored in depth.

Hypothalamic Grb10 enhances leptin signalling and promotes weight loss

Leptin acts on hypothalamic neurons expressing agouti-related protein (AgRP) or pro-opiomelanocortin (POMC) to suppress appetite and increase energy expenditure, but the intracellular mechanisms that modulate central leptin signalling are not fully understood. Here we show that growth factor receptor-bound protein 10 (Grb10), an adaptor protein that binds to the insulin receptor and negatively regulates its signalling pathway, can interact with the leptin receptor and enhance leptin signalling.

Increased fatty acid metabolism and decreased glycolysis are hallmarks of metabolic reprogramming within microglia in degenerating white matter during recovery from experimental stroke

The goal of this study was to evaluate changes in metabolic homeostasis during the first 12 weeks of recovery in a distal middle cerebral artery occlusion mouse model of stroke. To achieve this goal, we compared the brain metabolomes of ipsilateral and contralateral hemispheres from aged male mice up to 12 weeks after stroke to that of age-matched naïve and sham mice. There were 707 biochemicals detected in each sample by liquid chromatography-mass spectroscopy (LC-MS).

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