Life metabolism最新文献

The endocrine system is a fundamental type of long-range cell-cell communication that is important for maintaining metabolism, physiology, and other aspects of organismal homeostasis. Endocrine signaling is mediated by diverse blood-borne ligands, also called hormones, including metabolites, lipids, steroids, peptides, and proteins. The size and structure of these hormones are fine-tuned to make them bioactive, responsive, and adaptable to meet the demands of changing environments. Why has nature selected such diverse ligand types to mediate communication in the endocrine system? What is the chemical, signaling, or physiologic logic of these ligands? What fundamental principles from our knowledge of endocrine communication can be applied as we continue as a field to uncover additional new circulating molecules that are claimed to mediate long-range cell and tissue crosstalk? This review provides a framework based on the biochemical logic behind this crosstalk with respect to their chemistry, temporal regulation in physiology, specificity, signaling actions, and evolutionary development.

Postnatal growth retardation (PGR) frequently occurs during early postnatal development of piglets and induces high mortality. To date, the mechanism of PGR remains poorly understood. Adipose tissue-derived microbes have been documented to be associated with several disorders of metabolism and body growth. However, the connection between microbial disturbance of adipose tissue and pig PGR remains unclear. Here, we investigated piglets with PGR and found that the adipose tissue of PGR piglets was characterized by metabolism impairment, adipose abnormality, and specific enrichment of culturable bacteria from Proteobacteria. Gavage of Sphingomonas paucimobilis, a species of Sphingomonas genus from the alphaproteobacteria, induced PGR in piglets. Moreover, this bacterium could also lead to metabolic disorders and susceptibility to acute stress, resulting in weight loss in mice. Mechanistically, multi-omics analysis indicated the changes in lipid metabolism as a response of adipose tissue to abnormal microbial composition. Further experimental tests proved that one of the altered lipids phosphatidylethanolamines could rescue the metabolism disorder and growth retardation, thereby suppressing the amount of Sphingomonas in the adipose tissue. Together, these results highlight that the microbe-host crosstalk may regulate the metabolic function of adipose tissue in response to PGR.

Emerging evidence discloses the involvement of calcium channel protein in the pathological process of liver diseases. Transient receptor potential cation channel subfamily C member 3 (TRPC3), a ubiquitously expressed non-selective cation channel protein, controls proliferation, inflammation, and immune response via operating calcium influx in various organs. However, our understanding on the biofunction of hepatic TRPC3 is still limited. The present study aims to clarify the role and potential mechanism(s) of TRPC3 in alcohol-associated liver disease (ALD). We recently found that TRPC3 expression plays an important role in the disease process of ALD. Alcohol exposure led to a significant reduction of hepatic TRPC3 in patients with alcohol-related hepatitis (AH) and ALD models. Antioxidants (N-acetylcysteine and mitoquinone) intervention improved alcohol-induced suppression of TRPC3 via a miR-339-5p-involved mechanism. TRPC3 loss robustly aggravated the alcohol-induced hepatic steatosis and liver injury in mouse liver; this was associated with the suppression of Ca²⁺/calmodulin-dependent protein kinase kinase 2 (CAMKK2)/AMP-activated protein kinase (AMPK) and dysregulation of genes related to lipid metabolism. TRPC3 loss also enhanced hepatic inflammation and early fibrosis-like change in mice. Replenishing hepatic TRPC3 effectively reversed chronic alcohol-induced detrimental alterations in ALD mice. Briefly, chronic alcohol exposure-induced TRPC3 reduction contributes to the pathological development of ALD via suppression of the CAMKK2/AMPK pathway. Oxidative stress-stimulated miR-339-5p upregulation contributes to alcohol-reduced TRPC3. TRPC3 is the requisite and a potential target to defend alcohol consumption-caused ALD.