The metabolic adaptation in wild vertebrates via omics approaches

Metabolism is the basis for sustaining life and essential to the adaptive evolution of organisms.With the development of high-throughput sequencing technology,genetic mechanisms of adaptive evolution,including metabolic adaptation,have been extensively resolved by omics approaches,but a deep understanding of genetic and epigenetic metabolic adaptation is still lacking.Exploring metabolic adaptations from genetic and epigenetic perspectives in wild vertebrates is vital to understanding species evolution,especially for the early stages of adaptative evolution.Herein,we summarize the advances in our understanding of metabolic adaptations via omics approaches in wild vertebrates based on three types of cases:extreme environment,periodically changing environment,and changes of species characteristics.We conclude that the understanding of the formation of metabolic adaptations at the genetic level alone can well identify the adaptive genetic variation that has developed during evolution,but cannot resolve the potential impact of metabolic adaptations on the adaptative evolution in the future.Thus,it seems imperative to include epigenomics and metabolomics in the study of adaptation,and that in the future genomic and epigenetic data should be integrated to understand the formation of metabolic adaptation of wild vertebrate organisms.

Maternal low protein diet induces persistent expression changes in metabolic genes in male rats

BACKGROUND Perinatal exposure to a poor nutritional environment predisposes the progeny to the development of metabolic disease at the adult age,both in experimental models and humans.Numerous adaptive responses to maternal protein restriction have been reported in metabolic tissues.However,the expression of glucose/fatty acid metabolism-related genes in adipose tissue and liver needs to be described.AIM To evaluate the metabolic impact of perinatal malnutrition,we determined malnutrition-associated gene expression alterations in liver and adipose tissue.METHODS In the present study,we evaluated the alterations in gene expression of glycolytic/Krebs cycle genes(Pyruvate dehydrogenase kinase 4 and citrate synthase),adipogenic and lipolytic genes and leptin in the adipose tissue of offspring rats at 30 d and 90 d of age exposed to maternal isocaloric low protein(LP)diet throughout gestation and lactation.We also evaluated,in the livers of the same animals,the same set of genes as well as the gene expression of the transcription factors peroxisome proliferator-activated receptor gamma coactivator 1,forkhead box protein O1 and hepatocyte nuclear factor 4 and of gluconeogenic genes.RESULTS In the adipose tissue,we observed a transitory(i.e.,at 30 d)downregulation of pyruvate dehydrogenase kinase 4,citrate synthase and carnitine palmitoyl transferase 1b gene expression.Such transcriptional changes did not persist in adult LP rats(90 d),but we observed a tendency towards a decreased gene expression of leptin(P=0.052).The liver featured some gene expression alterations comparable to the adipose tissue,such as pyruvate dehydrogenase kinase 4 downregulation at 30 d and displayed other tissue-specific changes,including citrate synthase and fatty acid synthase upregulation,but pyruvate kinase downregulation at 30 d in the LP group and carnitine palmitoyl transferase 1b downregulation at 90 d.These gene alterations,together with previously described changes in gene expression in skeletal muscle,may account for the metabolic adaptations in response to maternal LP diet and highlight the occurrence of persistent transcriptional defects in key metabolic genes that may contribute to the development of metabolic alterations during the adult life as a consequence of perinatal malnutrition.CONCLUSION We conclude that perinatal malnutrition relays long-lasting transcriptional alterations in metabolically active organs,i.e.,liver and adipose tissue.

Fibroblast growth factor 21 in dairy cows:current knowledge and potential relevance

Fibroblast growth factor 21(FGF21)has been identified as an important regulator of carbohydrate and lipid metabolism,which plays an important role for metabolic regulation,particularly under conditions of energy deprivation or stress conditions.Dairy cows are subjected to a negative energy balance and various kinds of stress particularly during the periparturient phase and during early lactation.It has been shown that the plasma concentration of FGF21 in dairy cows is dramatically increased at parturition and remains high during the first weeks of lactation.This finding suggests that FGF21 might exert similar functions in dairy cows than in other species,such as mice or humans.However,the role of FGF21 in dairy cows has been less investigated so far.Following a brief summary of the previous findings about the function of FGF21 in humans and mice,the present review aims to present the current state of knowledge about the role of FGF21 in dairy cows.The first part of the review deals with the tissue localization of FGF21 and with conditions leading to an upregulation of FGF21 expression in the liver of dairy cows.In the second part,the influence of nutrition on FGF21 expression and the role of FGF21 for metabolic diseases in dairy cows is addressed.In the third part,findings of exogenous FGF21 application on metabolism in dairy cows are reported.Finally,the potential relevance of FGF21 in dairy cows is discussed.It is concluded that FGF21 might be of great importance for metabolic adaptation to negative energy balance and stress conditions in dairy cows.However,further studies are needed for a better understanding of the functions of FGF21 in dairy cows.

Time-dependent metabolomics uncover dynamic metabolic adaptions in MCF-7 cells exposed to bisphenol A

The biochemical consequences induced by xenobiotic stress are featured in dose-response and timeresolved landscapes.Understanding the dynamic process of cellular adaptations is crucial in conducting the risk assessment for chemical exposure.As one of the most phenotype-related omics,metabolome in response to environmental stress can vary from seconds to days.Up to now,very few dynamic metabolomics studies have been conducted to provide time-dependent mechanistic interpretations in understanding xenobiotics-induced cellular adaptations.This study aims to explore the time-resolved metabolite dysregulation manner and dynamically perturbed biological functions in MCF-7 cells exposed to bisphenol A(BPA),a well-known endocrine-disrupting chemical.By sampling at 11 time points from several minutes to hours,thirty seven significantly dysregulated metabolites were identified,ranging from amino acids,fatty acids,carboxylic acids and nucleoside phosphate compounds.The metabolites in different pathways basically showed distinct time-resolved changing patterns,while those within the common class or same pathways showed similar and synchronized dysregulation behaviors.The pathway enrichment analysis suggested that purine metabolism,pyrimidine metabolism,aminoacyl-tRNA biosynthesis as well as glutamine/glutamate(GABA)metabolism pathways were heavily disturbed.As exposure event continued,MCF-7 cells went through multiple sequential metabolic adaptations from cell proliferation to energy metabolism,which indicated an enhancing cellular requirement for elevated energy homeostasis,oxidative stress response and ER-αmediated cell growth.We further focused on the time-dependent metabolite dysregulation behavior in purine and pyrimidine metabolism,and identified the impaired glycolysis and oxidative phosphorylation by redox imbalance.Lastly,we established a restricted cubic splinebased model to fit and predict metabolite’s full range dysregulation cartography,with metabolite’sensitivity comparisons retrieved and novel biomarkers suggested.Overall,the results indicated that 8 h BPA exposure leaded to global dynamic metabolome adaptions including amino acid,nucleoside and sugar metabolism disorders,and the dysregulated metabolites with interfered pathways at different stages are of significant temporal distinctions.

Phenotypic changes in the metabolic profile and adiponectin activity during seasonal fattening and hibernation in female Daurian ground squirrels(Spermophilus dauricus)

Seasonal hibernation has provided an opportunity to study animals’phenotypic plasticity in adaptation to changing environment.In the present study focusing on the female Daurian ground squirrel(Spermophilus dauricus)-a well demonstrated seasonal hibernator-we examined their behavioral,morphological,and metabolic changes during fattening,hibernation,and emergence.Our data indicated high levels of food intake,fat deposition,and body mass increases during fattening compared to hibernation.The levels of serum glucose and triglycerides were also higher during fattening than during hibernation and emergence.Interestingly,although squirrels showed signs of obesity and elevated triglycerides in serum during fattening,triglyceride levels in the liver and skeletal muscles remained unchanged.Our data also indicated that adiponectin levels in serum and cerebrospinal fluid were different between fattening and hibernation.Levels of adiponectin receptor 1 in the skeletal muscle remained low during fattening but peaked in late hibernation.In contrast,adiponectin receptor 2 in the liver showed a steady increase during fattening,which was followed by a significant decrease at early hibernation.Our data indicate that adiponectin may play an important role in preventing heterotopic fat accumulation in a receptor-and organ-specific manner,as well as in facilitating the switch from glucose metabolism to lipid metabolism during fattening and hibernation in female Daurian ground squirrels.

CD4^(+)T cell metabolism,gut microbiota,and autoimmune diseases:implication in precision medicine of autoimmune diseases

CD4^(+)T cells are critical to the development of autoimmune disorders.Glucose,fatty acids,and glutamine metabolisms are the primary metabolic pathways in immune cells,including CD4^(+)T cells.The distinct metabolic programs in CD4^(+)T cell subsets are recognized to reflect the bioenergetic requirements,which are compatible with their functional demands.Gut microbiota affects T cell responses by providing a series of antigens and metabolites.Accumulating data indicate that CD4^(+)T cell metabolic pathways underlie aberrant T cell functions,thereby regulating the pathogenesis of autoimmune disorders,including inflammatory bowel diseases,systemic lupus erythematosus,and rheumatoid arthritis.Here,we summarize the current progress of CD4^(+)T cell metabolic programs,gut microbiota regulation of T cell metabolism,and T cell metabolic adaptions to autoimmune disorders to shed light on potential metabolic therapeutics for autoimmune diseases.