Sex-specific difference in intestinal glucose metabolism is associated with sexually dimorphic postprandial lactate shuttle and glucose homeostasis in mice.

Sexual dimorphism in glucose metabolism is increasingly recognized as a critical factor in metabolic homeostasis. Our prior study has highlighted the role of intestinal monocarboxylate transporter 1 (MCT1) in mediating lactate transport and its sex-specific effect on glucose metabolism in mice. Here, we investigated the sex-specific metabolic flux in the intestine and its impact on postprandial lactate shuttle and glucose homeostasis.

MCT1-mediated Lactate Shuttle to Mitochondria Governs Macrophage Polarization and Modulates Glucose Homeostasis by Affecting β Cells.

As a major fuel source for the tricarboxylic acid cycle, lactate controls energy metabolism through cell-to-cell or tissue-to-tissue lactate shuttles via monocarboxylate transporters (MCTs). Although lactate is shown to influence macrophage functions via histone lactylation, the specific functions of MCTs in macrophages remain incompletely understood. This study discovers that MCT1 and MCT4 have contrasting effects on regulating macrophage polarization.

SMYD2 inhibitors have no effect in improving non-alcoholic steatohepatitis in mice.

Introduction: Nonalcoholic steatohepatitis (NASH), characterized by progressive liver injury, inflammation, and fibrosis, is a leading chronic liver disease worldwide. Pharmacotherapy for NASH is thus urgently needed. Through a strategy of lineage tracing, it was recently discovered that deletion of a protein methyltransferase SMYD2 has a protective role in hepatic steatosis.

Short-term methionine deprivation inhibits TCA cycle and regulates macrophage polarization through uncharged tRNA and PDHA1 phosphorylation.

Methionine restriction diet has been extensively studied for its beneficial effects on metabolic health and aging. However, the impact of methionine deprivation on glucose metabolism per se and macrophage functions remains incompletely understood. In this study, we analyzed the functional roles of methionine deprivation on glucose flux and macrophage polarization.

Lactate transported by MCT1 plays an active role in promoting mitochondrial biogenesis and enhancing TCA flux in skeletal muscle.

Once considered as a "metabolic waste," lactate is now recognized as a major fuel for tricarboxylic acid (TCA) cycle. Our metabolic flux analysis reveals that skeletal muscle mainly uses lactate to fuel TCA cycle. Lactate is transported through the cell membrane via monocarboxylate transporters (MCTs) in which MCT1 is highly expressed in the muscle.

Glycogen synthesis is required for adaptive thermogenesis in beige adipose tissue and affects diet-induced obesity.

Glycogen is a form of energy storage for glucose in different tissues such as liver and skeletal muscle. It remains incompletely understood how glycogen impacts on adipose tissue functionality. Cold exposure elevated the expression of that encodes glycogen synthase 1 in brown adipose tissue (BAT) and inguinal white adipose tissue (iWAT).

PAQR9 regulates glucose homeostasis in diabetic mice and modulates insulin secretion in β cells in vitro under stress conditions.

Progesterone and adipoQ receptor 9 (PAQR9) is an endoplasmic reticulum (ER)-localized membrane protein that is involved in protein quality control of ER by interacting with BAG6. One of the physiological functions of PAQR9 is regulation of fasting-induced ketogenesis and fatty acid oxidation in the liver via modulating protein degradation of PPARα. However, it is currently unknown whether or not PAQR9 impacts glucose homeostasis.

Icariin Inhibits Intestinal Inflammation of DSS-Induced Colitis Mice Through Modulating Intestinal Flora Abundance and Modulating p-p65/p65 Molecule.

Background: Ulcerative colitis, as a kind of inflammatory bowel disease (IBD) is characterized by abdominal pain. This study aimed to investigate the effect of icariin (ICA) on the intestinal microflora of colitis mice.

Methods: Fifteen female C57BL/6 mice were randomly divided into the Control group, dextran sodium sulfate (DSS)-induced colitis (DSS) group, and ICA treatment (DSS+ICA) group.

CYP2C9, a Metabolic CYP450s Enzyme, Plays Critical Roles in Activating Ellagic Acid in Human Intestinal Epithelial Cells.

BACKGROUND The metabolic processing of ellagic acid (EA) by cytochrome P450s (CYP450s) expressed in the intestines is unclear. This study aimed to investigate the effects of CYP450s that are highly expressed in HIEC cells on metabolic activity of EA. MATERIAL AND METHODS HIEC cell models expressing 2B6, 2C9, 2D6, and 3A4 were generated by stably transfecting with CYP450 genes using a lentivirus system.