scholarly journals Signatures of mito-nuclear climate adaptation in a warbler species complex

2020 ◽  
Author(s):  
Silu Wang ◽  
Madelyn J. Ore ◽  
Else K. Mikkelsen ◽  
Julie Lee-Yaw ◽  
Sievert Rohwer ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Metabolic Pathways ◽  
Species Complex ◽  
Acid Metabolism ◽  
Climate Adaptation ◽  
Climatic Conditions ◽  
Secondary Contact ◽  
Mitochondrial Fatty Acid ◽  
Genetic Patterns

AbstractMitochondrial (mtDNA) and nuclear (nDNA) genes interact to govern metabolic pathways of mitochondria. When differentiated populations interbreed at secondary contact, incompatibilities between mtDNA of one population and nDNA of the other could result in low fitness of hybrids. Hermit Warblers (S. occidentalis abbreviated as HEWA) and inland Townsend’s Warblers (Setophaga townsendi, abbreviated as i-TOWA) exhibit distinct mtDNA haplotypes and a few nDNA regions of high differentiation, whereas coastal TOWA (c-TOWA) displays a mix of these genetic patterns consistent with ancient hybridization of HEWA and i-TOWA. Of the few highly-differentiated nDNA regions between i-TOWA and HEWA, two of these regions (on chromosome 5 and Z, respectively) are also differentiated between c-TOWA and i-TOWA, similar to the mtDNA pattern. These two nDNA regions are associated with mitochondrial fatty acid metabolism. Moreover, these nDNA regions are correlated with mtDNA ancestries among sites, a pattern consistent with mito-nuclear co-adaptation. Such mito-nuclear coevolution might be driven by climate-related selection, because the mito-nuclear ancestry is correlated with climatic conditions among sampling sites. These results suggest that cryptic differentiation in this species complex has been shaped by climate-correlated adaptation associated with mito-nuclear fatty acid metabolism.

scholarly journals Redox, amino acid, and fatty acid metabolism intersect with bacterial virulence in the gut

2018 ◽  
Vol 115 (45) ◽  
pp. E10712-E10719 ◽  
Author(s):  
Reed Pifer ◽  
Regan M. Russell ◽  
Aman Kumar ◽  
Meredith M. Curtis ◽  
Vanessa Sperandio
Keyword(s):  
Fatty Acid ◽  
High Throughput ◽  
Fatty Acid Metabolism ◽  
Metabolic Pathways ◽  
Virulence Genes ◽  
Acid Metabolism ◽  
Feedback Mechanism ◽  
Regulatory Pathways ◽  
Successful Infection ◽  
Cellular Circuits

The gut metabolic landscape is complex and is influenced by the microbiota, host physiology, and enteric pathogens. Pathogens have to exquisitely monitor the biogeography of the gastrointestinal tract to find a suitable niche for colonization. To dissect the important metabolic pathways that influence virulence of enterohemorrhagicEscherichia coli(EHEC), we conducted a high-throughput screen. We generated a dataset of regulatory pathways that control EHEC virulence expression under anaerobic conditions. This unraveled that the cysteine-responsive regulator, CutR, converges with the YhaO serine import pump and the fatty acid metabolism regulator FadR to optimally control virulence expression in EHEC. CutR activates expression of YhaO to increase activity of the YhaJ transcription factor that has been previously shown to directly activate the EHEC virulence genes. CutR enhances FadL, which is a pump for fatty acids that represses inhibition of virulence expression by FadR, unmasking a feedback mechanism responsive to metabolite fluctuations. Moreover, CutR and FadR also augment murine infection byCitrobacter rodentium, which is a murine pathogen extensively employed as a surrogate animal model for EHEC. This high-throughput approach proved to be a powerful tool to map the web of cellular circuits that allows an enteric pathogen to monitor the gut environment and adjust the levels of expression of its virulence repertoire toward successful infection of the host.

Abstract P028: Activation Of The Renin-angiotensin System Drives Renal Metabolic Abnormalities In Diabetic Nephropathy

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Kengo Azushima ◽  
Jean Paul Kovalik ◽  
Jianhong Ching ◽  
Susan B Gurley ◽  
Thomas M Coffman
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Renin Angiotensin System ◽  
Tca Cycle ◽  
High Grade ◽  
Wild Type ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Mitochondrial Fatty Acid

Activation of the renin-angiotensin system (RAS) is a major contributor to the pathogenesis of diabetic nephroathy (DN). However, the precise mechanisms of renoprotection associated with RAS blockade in DN are not entirely clear. The aim of this study is to examine whether metabolic effects of RAS blockade might contribute to renoprotection. We utilized a mouse model of DN combining severe type I diabetes (the Akita mutation) with a single-copy renin transgene (ReninTG) driven by the albumin promoter. Akita-ReninTG mice on a 129/Sv background (DN-susceptible mice) develop clinical features of human DN including high-grade albuminuria, renal interstitial inflammation and glomerulosclerosis, while Akita-ReninTG mice on a C57BL/6 background (DN-resistant mice) do not develop significant kidney disease. These two experimental groups were treated with the angiotensin receptor blocker (ARB) losartan 10 mg/kg/day for 12 weeks, and metabolic profiles in kidney tissues were examined using a targeted metabolomics assay. The DN-susceptible mice exhibited high-grade albuminuria that was significantly attenuated by ARB (Vehicle vs ARB: 1480±562 vs 193±42 μg/day, p =0.045), while DN-resistant mice had minimal albuminuria that was not affected by ARB (Vehicle vs ARB: 80±14 vs 75±14 μg/day, p =0.801). The metabolomics profiles of the DN-resistant mice were similar to C57BL/6 wild-type controls. By contrast, DN-susceptible mice exhibited broad reductions in even-chain acyl-carnitines and an abnormal profile of TCA cycle intermediates compared to 129/Sv wild-type controls, suggesting substantial impairments of renal mitochondrial fuel oxidation including altered fatty acid metabolism. RAS blockade had broad effects to correct this profile by increasing acetyl-carnitines generated from acetyl-CoA and concomitantly normalizing expression of genes associated with mitochondrial fatty acid metabolism including PPAR-α, PGC-1α, CPT1 and CPT2. ARB treatment restored TCA cycle activity to normal. These findings suggest that effects of RAS blockade re-establish normal fuel metabolism and mitochondrial fatty acid oxidation in kidney and may contribute to renoprotection.

ID: 81: NANOFORMULATED COPPER/ZINC SUPEROXIDE DISMUTASE CAUSES MUSCLE METABOLIC ALTERATIONS AND IMPROVES SYSTEMIC INSULIN SENSITIVITY IN MICE

2016 ◽  
Vol 64 (4) ◽  
pp. 927.1-927
Author(s):  
G Natarajan ◽  
C Perriotte-Olson ◽  
CV Desouza ◽  
S Viswanathan ◽  
D Manickam ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
De Novo ◽  
Tolerance Test ◽  
Copper Zinc Superoxide Dismutase ◽  
Zinc Superoxide Dismutase ◽  
Mitochondrial Fatty Acid ◽  
Copper Zinc

Oxidative stress mediates mitochondrial dysfunction and impairment of glucose metabolism in muscle thereby leading to systemic insulin resistance. In vivo studies have demonstrated that copper/zinc superoxide dismutase (Cu/ZnSOD)-deficient mice show oxidative damage in various organs including skeletal muscle. The objective of this study is to determine the role of nanoformulated Cu/ZnSOD (nanoSOD) in improving insulin sensitivity through effects inherent to muscle. Wild type mice were fed a standard chow diet for 10 weeks. A cohort of these mice received nanoSOD intraperitoneally at 1000 U/kg body weight once in two days for a period of 15 days. We noted that the fasting blood glucose level was significantly reduced in nanoSOD treated mice compared to control (P<0.05). Moreover, insulin tolerance test (ITT) revealed that nanoSOD treated mice showed improved glucose handling in response to insulin (0.75 U/kg body weight) compared to control mice. However, the response of these mice to acute glucose challenge as analyzed by glucose tolerance test was not different between groups. We next analyzed the muscle mRNA samples for genes involved in fatty acid metabolism. Interestingly, we noted that the expression of FASN and SREBP1, genes promoting fatty acid synthesis was significantly reduced in nanoSOD treated mice suggesting that de novo lipogenesis which can promote insulin resistance is reduced upon nanoSOD treatment. Further, the mRNA expression of PCX which promotes both gluconeogenesis and lipogenesis was significantly reduced (P<0.01) in nanoSOD treated mice compared to controls. Regarding genes regulating fatty acid metabolism, we noted that the expression of ACOX1, CPT1a, and CPT2, genes involved in mitochondrial fatty acid β-oxidation was reduced in nanoSOD treated mice. Interestingly, these metabolic changes were associated with reduced mRNA levels of inflammatory markers including TNFα, MMP12, and VCAM-1 in visceral adipose tissue in nanoSOD treated mice. However, in the liver, the mRNA level of genes involved in de novo lipogenesis and mitochondrial fatty acid β-oxidation was not altered upon nanoSOD treatment Taken together; our data demonstrate that nanoSOD improves systemic glucose handling which was associated with a reduction in de novo lipogenesis and fatty acid oxidation in muscle. Because fatty acid oversupply is a key mediator of muscle insulin resistance primarily via accumulation of fatty acid metabolites, our data suggest that changes in muscle fatty acid metabolism may play a role in mediating the effects of nanoSOD in improving systemic glucose handing and insulin resistance. .

scholarly journals Nitric Oxide Regulates Mitochondrial Fatty Acid Metabolism Through Reversible Protein S-Nitrosylation

2013 ◽  
Vol 6 (256) ◽  
pp. rs1-rs1 ◽  
Author(s):  
P.-T. Doulias ◽  
M. Tenopoulou ◽  
J. L. Greene ◽  
K. Raju ◽  
H. Ischiropoulos
Keyword(s):  
Nitric Oxide ◽  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Protein S ◽  
Mitochondrial Fatty Acid
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