Life metabolism最新文献

Efficient communication between the brain and peripheral organs is indispensable for regulating physiological function and maintaining energy homeostasis. The peripheral nervous system (PNS) in vertebrates, consisting of the autonomic and somatic nervous systems, bridges the peripheral organs and the central nervous system (CNS). Metabolic signals are processed by both vagal sensory nerves and somatosensory nerves. The CNS receives sensory inputs via ascending nerves, serves as the coordination and integration center, and subsequently controls internal organs and glands via descending nerves. The autonomic nervous system consists of sympathetic and parasympathetic branches that project peripheral nerves into various anatomical locations to regulate the energy balance. Sympathetic and parasympathetic nerves typically control the reflexive and involuntary functions in organs. In this review article, we outline the innervation of adipose tissue, gut, pancreas, and liver, to illustrate the neurobiological basis of central-peripheral interactions. We emphasize the importance of understanding the functional atlas of neural control of energy metabolism, and more importantly, provide potential avenues for further research in this area.

Diet plays a substantial role in the etiology, progression, and treatment of chronic disease and is best considered as a multifaceted set of modifiable input variables with pleiotropic effects on a variety of biological pathways spanning multiple organ systems. This brief review discusses key issues related to the design and conduct of diet interventions in rodent models of metabolic disease and their implications for interpreting experiments. We also make specific recommendations to improve rodent diet studies to help better understand the role of diet on metabolic physiology and thereby improve our understanding of metabolic disease.

The continuous emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants led to a rapid decline in protection efficacy and neutralizing titers even after three doses of COVID-19 vaccines. Here, we report an open-labeled Phase I clinical trial of a modified mRNA vaccine (SYS6006) as a fourth-dose booster in healthy adults. Eighteen eligible participants, who had completed three doses of inactivated COVID-19 vaccines, received a fourth boosting dose of SYS6006-20 μg. Eighteen convalescent COVID-19 patients were enrolled for the collection of serum samples as a comparator of immunogenicity. The primary endpoint of this trial was titers of anti-receptor binding domain of spike glycoprotein (RBD) antibodies of the Omicron strain (BA.2 and BA.4/5) in serum; titers of neutralizing antibodies against pseudovirus of the Omicron strain (BA.2 and BA.4/5). The secondary endpoint was the incidence of adverse events within 30 days after the boosting. The exploratory endpoint was the cellular immune responses (interferon gamma, IFN-γ). This trial was registered with the Chinese Clinical Trial Registry website. No serious adverse events were reported within 30 days after vaccination. No Grade 3 fever or serious adverse event was reported in the SYS6006 group. Notably, SYS6006 elicited higher titers and longer increases in anti-RBD antibodies and neutralizing antibodies (>90 days) compared with the convalescent group (P < 0.0001) against Omicron strain (BA.2 and BA.4/5). Besides, higher positive spots of T-cell-secreting IFN-γ were observed in the SYS6006 group than those in the convalescent group (P < 0.05). These data demonstrated that SYS6006 was well tolerated and highly immunogenic, generating a stronger and more durable immune response against different variants of SARS-CoV-2.

The thermogenic brown and beige adipocytes consume fatty acids and generate heat to maintain core body temperature in the face of cold challenges. Since their validated presence in humans, the activation of thermogenic fat has been an attractive target for treating obesity and related metabolic diseases. Here, we reported that the opioid growth factor receptor (Ogfr) was highly expressed in adipocytes and promoted thermogenesis. The mice with genetic deletion of Ogfr in adipocytes displayed an impaired capacity to counter environmental cold challenges. Meanwhile, Ogfr ablation in adipocytes led to reduced fatty acid oxidation, enhanced lipid accumulation, impaired glucose tolerance, and exacerbated tissue inflammation under chronic high-fat diet (HFD)-fed conditions. At the cellular level, OGFr enhanced the production of mitochondrial trifunctional protein subunit α (MTPα) and also interacted with MTPα, thus promoting fatty acid oxidation. Together, our study demonstrated the important role of OGFr in fatty acid metabolism and adipose thermogenesis.

Weight loss from an overweight state is associated with a disproportionate decrease in whole-body energy expenditure that may contribute to the heightened risk for weight regain. Evidence suggests that this energetic mismatch originates from lean tissue. Although this phenomenon is well documented, the mechanisms have remained elusive. We hypothesized that increased mitochondrial energy efficiency in skeletal muscle is associated with reduced expenditure under weight loss. Wildtype (WT) male C57BL6/N mice were fed with high fat diet for 10 weeks, followed by a subset of mice that were maintained on the obesogenic diet (OB) or switched to standard chow to promote weight loss (WL) for additional 6 weeks. Mitochondrial energy efficiency was evaluated using high-resolution respirometry and fluorometry. Mass spectrometric analyses were employed to describe the mitochondrial proteome and lipidome. Weight loss promoted ~50% increase in the efficiency of oxidative phosphorylation (ATP produced per O₂ consumed, or P/O) in skeletal muscle. However, weight loss did not appear to induce significant changes in mitochondrial proteome, nor any changes in respiratory supercomplex formation. Instead, it accelerated the remodeling of mitochondrial cardiolipin (CL) acyl-chains to increase tetralinoleoyl CL (TLCL) content, a species of lipids thought to be functionally critical for the respiratory enzymes. We further show that lowering TLCL by deleting the CL transacylase tafazzin was sufficient to reduce skeletal muscle P/O and protect mice from diet-induced weight gain. These findings implicate skeletal muscle mitochondrial efficiency as a novel mechanism by which weight loss reduces energy expenditure in obesity.