Leptin signaling maintains autonomic stability during severe influenza infection
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PROVIDER: PRJNA1147219 | ENA |
REPOSITORIES: ENA
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Project description:Leptin is a pleiotropic hormone that is released by adipocytes and tightly controls energy balance by regulating a range of physiological processes. While leptin is best known for signaling through the hypothalamic arcuate nucleus to regulate feeding, it also supports the immune system by binding its cognate receptor Ob-R to activate various immunocyte populations. Indeed, patients with congenital leptin or leptin receptor deficiency not only display severe obesity but also exhibit increased mortality from infections. Leptin supplementation to leptin deficient mice and humans increases CD4+ cell numbers and augments proinflammatory Th1 responses ex vivo. However, whether this leptin-induced immune response is necessary for viral clearance in vivo is unknown. To better delineate the role of leptin in infection, we inoculated leptin deficient ob/ob mice with influenza and acutely supplemented leptin in physiologically relevant doses prior to infection. Although ob/ob mice and diet-induced obese (DIO) mice have comparable levels of insulin resistance and adiposity, a sublethal dose of influenza virus in DIO mice causes mortality in approximately 80% of ob/ob mice, which was completely reversed by leptin supplementation. Serum cytokine profiling and whole tissue RNA sequencing of spleen, lung, and visceral adipose tissue demonstrated increased inflammatory and anti-viral responses in leptin-supplemented mice and no signs of excessive immunopathology in either group. Further flow cytometric analysis indicated an elevated Th1 immune response locally and systemically in leptin-supplemented mice, along with a two-fold increase in spleen sizes and an expansion in the proportion of splenic B cells. Despite augmented anti-viral responses in leptin-supplemented mice, leptin deficient ob/ob mice were equally capable of clearing the virus. Moreover, pulse oximetry showed diminished oxygen saturation in both groups, a finding further corroborated by similar levels of histopathologic lung damage. Interestingly, leptin-supplementation in ob/ob mice prevented profound hypothermia and bradycardia, which occurred prior to death in control ob/ob mice. Taken together, we provide evidence that leptin is dispensable for immunologic control of viral infection and may instead confer a survival benefit by maintaining autonomic stability. These findings open new avenues for research on the role of leptin signaling in infection.
2024-12-30 | GSE274568 | GEO
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Project description:Leptin monotherapy (i.e. without the use of administered insulin and/or any other molecule) corrects ID-induced metabolic aberrancies and promotes survival of insulin deficient rodents. These results generated great interest in the possibility of treating insulin deficient patients with leptin and/or molecule(s) underlying its beneficial effects. Hence, with the goal of identifying circulating molecule(s) underlying the advantageous effect of leptin we performed quantitative proteomic analysis of plasma and identified S100A9 as a putative peripheral mediator of leptin action. Here, to identify circulating molecule(s) underlying the advantageous effect of leptin we compared the results obtained by quantitative proteomic analysis of plasma between 2 groups of mice: streptozotocin (STZ)-treated mice that underwent intracerebroventricular (icv) leptin treatment for 12 days (STZ-Leptin) and ii) STZ-treated mice that underwent icv leptin treatment for 10 days and were withdrawn from leptin treatment for the following two days (STZ-Leptin-STOP). STZ treatment led to a massive loss of pancreatic insulin-producing β-cells, diminished pancreatic Proinsulin mRNA level, and caused severe insulinopenia, and hyperglycemia. icv leptin administration normalized hyperglycemia. However, two days after leptin delivery was halted hyperglycemia reappeared. We hypothesized that change in plasmatic protein(s) content could underlie re-emergence of hyperglycemia following decrease of leptin action.
2019-07-12 | PXD013466 | Pride
Project description:Autonomic nervous system is widely distributed in liver, and some reserchers have found that disruppted autonomic nerves will delay liver regeneration. We used microarrays to further highlight the regulatory role of autonomic nervous system in liver regeneration at gene transcription level. Surgical operations of rat partial hepatectomy (PH) and its operation control (OC), sympathectomy combining partial hepatectomy (SPH), vagotomy combining partial hepatectomy (VPH), and total liver denervation combining partial hepatectomy (TDPH) were performed, and the expression profiles of regenerating liver at 2h were detected using Rat Genome 230 2.0 array. Then the significantly changed genes related to liver regeneration (LR)-, injury-, splanchnic nerve-LR-, vagal nerve-LR-, and autonomic nerve-LR-related genes were identified, respectively. The relevance of gene expression profiles and biological processes was analyzed by bioinformatics and systems biology.
2010-12-18 | E-GEOD-26138 | biostudies-arrayexpress
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Project description:Autonomic nervous system is widely distributed in liver, and some reserchers have found that disruppted autonomic nerves will delay liver regeneration. We used microarrays to further highlight the regulatory role of autonomic nervous system in liver regeneration at gene transcription level.
2010-12-18 | GSE26138 | GEO
Project description:Caloric Restriction in Leptin Deficiency Worsens Myocardial Steatosis: Failure to Upregulate PPAR gamma and Thermogenic Glyecrolipid/Fatty Acid Cycling Growing evidence supports an anti-lipotoxic role for leptin in preventing inappropriate peripheral tissue lipid deposition. Obese, leptin deficient ob/ob mice develop left ventricular (LV) hypertrophy and myocardial steatosis with increased apoptosis and decreased longevity. Here we investigated the cardiac effects of caloric restriction in leptin deficiency. Echocardiography was performed on C57Bl/6 wild-type mice (WT) and 7-month-old ob/ob mice fed ad lib, leptin-repleted (LR-ob/ob), or calorie-restricted (CR-ob/ob) for four weeks. Ventricular tissue was examined by electron microscopy (EM), mitochondrial coupling assay, and microarray expression profiling. LR and CR-ob/ob mice showed decreased body weight, heart weight, and LV wall thickness compared to ad lib ob/ob mice. LV fractional shortening was decreased in ad lib ob/ob mice, but restored to WT levels in LR and CR groups. However, EM revealed severe cardiac steatosis in the CR-ob/ob group compared to only moderate steatosis in ad lib ob/ob . Despite marked cardiac steatosis, CR (like LR) restored mitochondrial coupling to WT levels. CR up-regulated genes associated with oxidative stress and cell death, changes suggestive of cardiac lipotoxicity. LR, but not CR was shown to induce core genes involved in glycerolipid/free fatty acid cycling, a highly thermogenic pathway that can reduce intracellular lipid stores. LR, but not CR up-regulated and restored PGC1 and PPARto wild type levels; CR paradoxically further suppressed cardiac PPAR. Thus, leptin is essential in protecting the heart from lipotoxicity, and the inability to up-regulate the thermogenic glycerolipid/free fatty acid cycling pathway may impair the response of leptin deficient animals to the lipotoxic stress of calorie restriction. 6 month aged ob/ob mice were either leptin repleted with osmotic mini-pumps, calorie restricted to match the caloric intake of the leptin repleted mice, or fed ad lib for one month. 6-8 month C57Bl/6J mice were aged to serve as controls.
2011-04-29 | E-GEOD-16790 | biostudies-arrayexpress
Project description:Endothelial cell senescence is an accomplice for vascular aging, which leads to cardiovascular diseases (CVD). Evidences showed that Hippo- Yes-associated protein (YAP) signaling pathway plays an essential role in aging-associated CVD. However, the exact role of YAP protein in endothelial cell senescence remains not fully clear. Here, we reported that YAP was elevated in senescent human umbilical vein endothelial cells (HUVECs) and inhibition of YAP by either specific siRNAs or inhibitor Verteporfin could attenuate HUVECs senescence. In contrast, overexpression of YAP induces cell senescence. Besides, we found that UFMylation activity and YAP were both elevated in senescent cells. Mechanistically, we found that UFMylation, a newly identified ubiquitin-like modification with essential biological functions, maintains the stability of YAP and further found that YAP is a substrate for UFMylation. Importantly, we found that compound 8.5, an inhibitor of E1 of UFMylation, can attenuate cell senescence with reduced YAP protein and alleviate vascular aging and improve cardiac function in aged mice. Therefore, compound 8.5 may be a potential small molecule for delaying vascular aging. Together, our finding provides molecular mechanism by which UFMylation maintains YAP stability and exerts an important role in promoting cell senescence, and identified that a previously unrecognized UFMylation is a potential therapeutic target for anti-aging.
2025-01-08 | GSE273828 | GEO
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