Molecular Metabolism

OBJECTIVE: The peroxisome proliferator-activated receptor α (PPARα) is a transcription factor driving target genes involved in fatty acid β-oxidation. To what extent various PPARα interacting proteins may assist its function as a transcription factor is incompletely understood. An ORFeome-wide unbiased mammalian protein-protein interaction trap (MAPPIT) using PPARα as bait revealed a PPARα-ligand-dependent interaction with the orphan nuclear receptor estrogen-related receptor α (ERRα)...

Metamorphosis is a transition from growth to reproduction, through which an animal adopts adult behavior and metabolism. Yet the neural mechanisms underlying the switch is unclear. Here we report that neuronal E93, a transcription factor essential for metamorphosis, regulates the adult metabolism, physiology, and behavior in Drosophila melanogaster. Identified from a screen designed to find new neuronal regulators of metabolism, E93 is required to control appetite, metabolism, exercise endurance, and circadian rhythms...

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OBJECTIVES: During fasting, liver pivotally regulates blood glucose levels through glycogenolysis and gluconeogenesis. Kidney also produces glucose through gluconeogenesis. Gluconeogenic genes are transactivated by fasting, but their expression patterns are chronologically different between the two organs. We find that renal gluconeogenic gene expressions are positively correlated with the blood β-hydroxybutyrate concentration. Thus, we herein aim to investigate the regulatory mechanism and its physiological implications...

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BACKGROUND: Ceramides are sphingolipids that act as signaling molecules involved in regulating cellular processes including apoptosis, proliferation, and metabolism. Deregulation of ceramide metabolism contributes to cancer development and progression. Therefore, regulation of ceramide levels in cancer cells is being explored as a new approach for cancer therapy. SCOPE OF THE REVIEW: This review discusses the multiple roles of ceramides in cancer cells and strategies to modulate ceramide levels for cancer therapy...

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common complication of obesity and in severe cases progresses to metabolic dysfunction-associated steatohepatitis (MASH). Small heterodimer partner (SHP) is an orphan member of the nuclear receptor superfamily and regulates metabolism and inflammation in the liver via a variety of pathways. In this study, we investigate the molecular foundation of MASH progression in mice with hepatic SHP deletion and explore possible therapeutic means to reduce MASH...

OBJECTIVE: Alström Syndrome (AS), caused by biallelic ALMS1 mutations, includes obesity with disproportionately severe insulin resistant diabetes, dyslipidemia, and fatty liver. Prior studies suggest that hyperphagia is accounted for by loss of ALMS1 function in hypothalamic neurones, whereas disproportionate metabolic complications may be due to impaired adipose tissue expandability. We tested this by comparing the metabolic effects of global and mesenchymal stem cell (MSC)-specific Alms1 knockout...

OBJECTIVE: Tumour progression drives profound alterations in host metabolism, such as adipose tissue depletion, an early event of cancer cachexia. As fatty acid consumption by cancer cells increases upon acidosis of the tumour microenvironment, we reasoned that fatty acids derived from distant adipose lipolysis may sustain tumour fatty acid craving, leading to the adipose tissue loss observed in cancer cachexia. METHODS: To evaluate the pro-lipolytic capacities of acid-exposed cancer cells, primary mouse adipocytes from subcutaneous and visceral adipose tissue were exposed to pH-matched conditioned medium from human and murine acid-exposed cancer cells (pH 6...

OBJECTIVE: Ketone bodies (such as β-hydroxybutyrate or BHB) have been recently proposed as signals involved in brain regulation of energy homeostasis and obesity development. However, the precise role of ketone bodies sensing by the brain, and its impact on metabolic disorder development remains unclear. Nevertheless, partial deletion of the ubiquitous ketone bodies transporter MCT1 in mice (HE mice) results in diet-induced obesity resistance, while there is no alteration under normal chow diet...

BACKGROUND: Hepatic insulin resistance, which leads to increased hepatic gluconeogenesis, is a major contributor to fasting hyperglycemia in type 2 diabetes mellitus (T2DM). However, the mechanism of impaired insulin-dependent suppression of hepatic gluconeogenesis remains elusive. Delta/Notch-like epidermal growth factor (EGF)-related receptor (DNER), firstly described as a neuron-specific Notch ligand, has been recently identified as a susceptibility gene for T2DM through genome-wide association studies...

OBJECTIVE: Estrogen-related-receptor α (ERRα) plays a critical role in the transcriptional regulation of cellular bioenergetics and metabolism, and perturbations in its activity have been associated with metabolic diseases. While several coactivators and corepressors of ERRα have been identified to date, a knowledge gap remains in understanding the extent to which ERRα cooperates with coregulators in the control of gene expression. Herein, we mapped the primary chromatin-bound ERRα interactome in mouse liver...

Identification of new mechanisms mediating insulin sensitivity is important to allow validation of corresponding therapeutic targets. In this study, we first used a cellular model of skeletal muscle cell iron overload and found endoplasmic reticulum (ER) stress and insulin resistance occurred after iron treatment. Insulin sensitivity was assessed using cells engineered to express an Akt biosensor, based on nuclear FoxO localization, as well as western blotting for insulin signaling proteins. Use of salubrinal to elevate eIF2α phosphorylation and promote the unfolded protein response (UPR) attenuated iron-induced insulin resistance...

OBJECTIVE: Theut microbiota increases energy availability through fermentation of dietary fibers to short-chain fatty acids in conventionally raised mice. Energy deficiency in germ-free (GF) mice increases glucagon-like peptide-1 (GLP-1) levels, which slows intestinal transit. To further analyze the role of GLP-1-mediated signaling in this model of energy deficiency, we re-derived mice lacking GLP-1 receptor (GLP-1R KO) as GF. METHODS: GLP-1R KO mice were rederived as GF through hysterectomy and monitored for 30 weeks...

OBJECTIVE: Evaluation of mitochondrial oxygen consumption and ATP production is important to investigate pancreatic islet pathophysiology. Most studies use cell lines due to difficulties in measuring primary islet respiration, which requires specific equipment and consumables, is expensive and poorly reproducible. Our aim was to establish a practical method to assess primary islet metabolic fluxes using standard commercial consumables. METHODS: Pancreatic islets were isolated from mice/rats, dispersed with trypsin, and adhered to pre-coated standard Seahorse or Resipher microplates...

OBJECTIVES: We have previously shown that lactate is an essential metabolite for macrophage polarisation during ischemia-induced muscle regeneration. Recent in vitro work has implicated histone lactylation, a direct derivative of lactate, in macrophage polarisation. Here, we explore the in vivo relevance of histone lactylation for macrophage polarisation after muscle injury. METHODS: To evaluate macrophage dynamics during muscle regeneration, we subjected mice to ischemia-induced muscle damage by ligating the femoral artery...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

OBJECTIVE: In the small intestine, the products of digestion of dietary triacylglycerol (TAG), fatty acids (FA) and monoacylglycerol, are taken up by absorptive cells, enterocytes, for systemic energy delivery. These digestion products can also bind receptors on endocrine cells to stimulate the release of hormones capable of influencing systemic energy metabolism. The initial phase of intestinal FA absorption involves the acylation of FAs to acyl-CoA by the acyl-CoA long chain synthetase (ACSL) enzymes...

No abstract text is available yet for this article.