However, leptin functions in early development of vertebrates are largely unknown. Leptin and leptin receptor ( lepr) are highly conserved and share extensive homology across vertebrates including all mammals and fish and have been studied in many model organisms. Using a combination of metabolomics and transcriptomics, a recent published paper demonstrates that the carbohydrate, lipid and amino acid metabolic liver responses to glucose administration are broadly different between wild type and ob/ob mice. showed that leptin mediates a glucose-fatty acid cycle to maintain glucose homeostasis in starvation in rats. Using a positional isotopomer NMR tracer analysis method, Perry et al. Several studies have shown metabolic disorders in ob/ob mice, db/db mice and obese Zucker rats measured by mass spectrometry (MS) or 1H solution nuclear magnetic resonance (NMR). Similar to the rare cases of congenital human leptin deficiency, these rodent mutants display hyperphagia, obesity and an insulin resistant phenotype. Leptin signaling deficient rodent mutants, such as ob/ob mice, db/db mice and Zucker rats, have been commonly used as animal models in leptin studies. Metabolic effects of leptin have been studied in rodent animal models. Leptin administration therapy with metreleptin, a recombinant human leptin analogue, has been approved for the treatment of the metabolic abnormalities linked to dyslipidemia. Congenital leptin deficiency in humans results in extreme obesity, hyperphagia and many complications such as type 2 diabetes. Leptin, the first discovered adipokine, plays a critical role in the regulation of energy balance and homeostasis of metabolism. In addition, by studying the transcriptome, we found similar changes in gene regulation related to proteolysis and arachidonic acid metabolism in these two different in vivo models. These metabolic changes show similar features as observed during progression of tuberculosis in human patients, mice and zebrafish larvae. Leptin deficiency leads to highly similar metabolic alterations in metabolites in both mice and zebrafish larvae. Deep sequencing showed that many genes involved in proteolysis and arachidonic acid metabolism were dysregulated in ob/ob mice heads and lepb mutant zebrafish larvae compared to their wild type controls, respectively. Moreover, we also observed that glucose and lipid levels were increased in lepb −/− zebrafish larvae compared to the lepb +/+ group. Thirteen metabolites were identified as common biomarkers discriminating ob/ob mice and lepb −/− zebrafish larvae from their respective wild type controls: alanine, citrulline, ethanolamine, glutamine, glycine, histidine, isoleucine, leucine, methionine, phenylalanine, putrescine, serine and threonine. For transcriptome studies, deep RNA sequencing was used. Different metabolomic approaches including mass spectrometry, nuclear magnetic resonance (NMR) and high-resolution magic-angle-spinning NMR spectrometry were used to investigate the metabolic changes caused by leptin deficiency in mutant ob/ob adult mice and lepb −/− zebrafish larvae. This study aims to explore the effects of leptin in mice and zebrafish larvae by integration of metabolomics and transcriptomics. However, the molecular mechanism and cross talks between leptin and metabolic pathways leading to metabolic homeostasis across different species are not clear. Leptin plays a critical role in the regulation of metabolic homeostasis.
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