RESUMO
Researchers from diverse disciplines, including organismal and cellular physiology, sports science, human nutrition, evolution and ecology, have sought to understand the causes and consequences of the surprising variation in metabolic rate found among and within individual animals of the same species. Research in this area has been hampered by differences in approach, terminology and methodology, and the context in which measurements are made. Recent advances provide important opportunities to identify and address the key questions in the field. By bringing together researchers from different areas of biology and biomedicine, we describe and evaluate these developments and the insights they could yield, highlighting the need for more standardisation across disciplines. We conclude with a list of important questions that can now be addressed by developing a common conceptual and methodological toolkit for studies on metabolic variation in animals.
Assuntos
Metabolismo Basal , Animais , Humanos , FenótipoRESUMO
Heart failure is among the first major consequences of heat stress in aquatic ectotherms. Mitochondria produce most of the ATP used by the heart and represent almost half of the volume in cardiac cells. It has therefore been hypothesized that mitochondrial dysfunctions may be highly involved in heart failure associated with heat stress. The present study aims to investigate if CTmax is linked to the thermal sensitivity of three-spined sticklebacks' (G. aculeatus) cardiac mitochondria, and if it is influenced by heart fatty acid composition and age. To do so, we measured the CTmax of 30 fish. The cardiac mitochondrial oxygen consumption was measured by high resolution respirometry at three temperatures and heart lipid profiles were obtained by Gas chromatography (GC) coupled with a Flame Ionization Detector (FID). Fish age was estimated via otolith readings. Fatty acid profiles showed no correlation with CTmax, but EPA levels were higher in older individuals. Mitochondrial respiration was measured in 35 fish using high resolution respirometry. It was strongly affected by temperature and showed a drastic drop in OXPHOS respiration fed by Complex I and Complex I+II, while uncoupled respiration plateaued at CTmax temperature. Our results suggest that Complex I is an important modulator of the impact of temperature on mitochondrial respiration at high temperatures but is not the main limiting factor in physiological conditions (maximal OXPHOS). Mitochondrial respiration was also affected by fish age, showing a general decrease in older individuals.
RESUMO
Species with a wide distribution can experience significant regional variation in environmental conditions, to which they can acclimatize or adapt. Consequently, the geographic origin of an organism can influence its responses to environmental changes, and therefore its sensitivity to combined global change drivers. This study aimed at determining the physiological responses of the northern shrimp, Pandalus borealis, at different levels of biological organization and from four different geographic origins, exposed to elevated temperature and low pH to define its sensitivity to future ocean warming and acidification. Shrimp sampled within the northwest Atlantic were exposed for 30 days to combinations of three temperature (2, 6 or 10°C) and two pH levels (7.75 or 7.40). Survival, metabolic rates, whole-organism aerobic performance and cellular energetic capacity were assessed at the end of the exposure. Our results show that shrimp survival was negatively affected by temperature above 6°C and low pH, regardless of their origin. Additionally, shrimp from different origins show overall similar whole-organism performances: aerobic scope increasing with increasing temperature and decreasing with decreasing pH. Finally, the stability of aerobic metabolism appears to be related to cellular adjustments specific to shrimp origin. Our results show that the level of intraspecific variation differs among levels of biological organization: different cellular capacities lead to similar individual performances. Thus, the sensitivity of the northern shrimp to ocean warming and acidification is overall comparable among origins. Nonetheless, shrimp vulnerability to predicted global change scenarios for 2100 could differ among origins owing to different regional environmental conditions.
Assuntos
Crustáceos , Água do Mar , Animais , Temperatura , Concentração de Íons de Hidrogênio , Água do Mar/química , Oceanos e Mares , Aquecimento GlobalRESUMO
We investigated the role of mitochondrial function in the avian thermoregulatory response to a cold environment. Using black-capped chickadees (Poecile atricapillus) acclimated to cold (-10°C) and thermoneutral (27°C) temperatures, we expected to observe an upregulation of pectoralis muscle and liver respiratory capacity that would be visible in mitochondrial adjustments in cold-acclimated birds. We also predicted that these adjustments would correlate with thermogenic capacity (Msum) and basal metabolic rate (BMR). Using tissue high-resolution respirometry, mitochondrial performance was measured as respiration rate triggered by proton leak and the activity of complex I (OXPHOSCI) and complex I+II (OXPHOSCI+CII) in the liver and pectoralis muscle. The activity of citrate synthase (CS) and cytochrome c oxidase (CCO) was also used as a marker of mitochondrial density. We found 20% higher total CS activity in the whole pectoralis muscle and 39% higher total CCO activity in the whole liver of cold-acclimated chickadees relative to that of birds kept at thermoneutrality. This indicates that cold acclimation increased overall aerobic capacity of these tissues. Msum correlated positively with mitochondrial proton leak in the muscle of cold-acclimated birds while BMR correlated with OXPHOSCI in the liver with a pattern that differed between treatments. Consequently, this study revealed a divergence in mitochondrial metabolism between thermal acclimation states in birds. Some functions of the mitochondria covary with thermogenic capacity and basal maintenance costs in patterns that are dependent on temperature and body mass.
Assuntos
Metabolismo Basal , Aves Canoras , Aclimatação/fisiologia , Animais , Metabolismo Basal/fisiologia , Temperatura Baixa , Mitocôndrias/metabolismo , Músculos Peitorais/metabolismo , Prótons , Aves Canoras/fisiologiaRESUMO
Doubly uniparental inheritance (DUI) represents a notable exception to the general rule of strict maternal inheritance (SMI) of mitochondria in metazoans. This system entails the coexistence of two mitochondrial lineages (F- and M-type) transmitted separately through oocytes and sperm, thence providing an unprecedented opportunity for the mitochondrial genome to evolve adaptively for male functions. In this study, we explored the impact of a sex-specific mitochondrial evolution upon gamete bioenergetics of DUI and SMI bivalve species, comparing the activity of key enzymes of glycolysis, fermentation, fatty acid metabolism, tricarboxylic acid cycle, oxidative phosphorylation and antioxidant metabolism. Our findings suggest reorganized bioenergetic pathways in DUI gametes compared to SMI gametes. This generally results in a decreased enzymatic capacity in DUI sperm with respect to DUI oocytes, a limitation especially prominent at the terminus of the electron transport system. This bioenergetic remodelling fits a reproductive strategy that does not require high energy input and could potentially link with the preservation of the paternally transmitted mitochondrial genome in DUI species. Whether this phenotype may derive from positive or relaxed selection acting on DUI sperm is still uncertain.
Assuntos
Bivalves , Genoma Mitocondrial , Animais , Bivalves/genética , DNA Mitocondrial/genética , Feminino , Masculino , Mitocôndrias/genética , Fosforilação OxidativaRESUMO
Star-nosed moles (Condylura cristata) have an impressive diving performance and burrowing lifestyle, yet no ventilatory data are available for this or any other talpid mole species. We predicted that, like many other semi-aquatic and fossorial small mammals, star-nosed moles would exhibit: (i) a blunted (i.e. delayed or reduced) hypoxic ventilatory response, (ii) a reduced metabolic rate and (iii) a lowered body temperature (Tb) in hypoxia. We thus non-invasively measured these variables from wild-caught star-nosed moles exposed to normoxia (21% O2) or acute graded hypoxia (21-6% O2). Surprisingly, star-nosed moles did not exhibit a blunted HVR or decreased Tb in hypoxia, and only manifested a significant, albeit small (<8%), depression of metabolic rate at 6% O2 relative to normoxic controls. Unlike small rodents inhabiting similar niches, star-nosed moles are thus intolerant to hypoxia, which may reflect an evolutionary trade-off favouring the extreme sensory biology of this unusual insectivore.
Assuntos
Mergulho , Toupeiras , Animais , Temperatura Corporal , Eulipotyphla , HipóxiaRESUMO
The oxidative phosphorylation (OxPhos) pathway is responsible for most aerobic ATP production and is the only pathway with both nuclear and mitochondrial encoded proteins. The importance of the interactions between these two genomes has recently received more attention because of their potential evolutionary effects and how they may affect human health and disease. In many different organisms, healthy nuclear and mitochondrial genome hybrids between species or among distant populations within a species affect fitness and OxPhos functions. However, what is less understood is whether these interactions impact individuals within a single natural population. The significance of this impact depends on the strength of selection for mito-nuclear interactions. We examined whether mito-nuclear interactions alter allele frequencies for ~11,000 nuclear SNPs within a single, natural Fundulus heteroclitus population containing two divergent mitochondrial haplotypes (mt-haplotypes). Between the two mt-haplotypes, there are significant nuclear allele frequency differences for 349 SNPs with a p-value of 1% (236 with 10% FDR). Unlike the rest of the genome, these 349 outlier SNPs form two groups associated with each mt-haplotype, with a minority of individuals having mixed ancestry. We use this mixed ancestry in combination with mt-haplotype as a polygenic factor to explain a significant fraction of the individual OxPhos variation. These data suggest that mito-nuclear interactions affect cardiac OxPhos function. The 349 outlier SNPs occur in genes involved in regulating metabolic processes but are not directly associated with the 79 nuclear OxPhos proteins. Therefore, we postulate that the evolution of mito-nuclear interactions affects OxPhos function by acting upstream of OxPhos.
Assuntos
Núcleo Celular/genética , Evolução Molecular , Fundulidae/genética , Mitocôndrias/genética , Transporte Ativo do Núcleo Celular/genética , Animais , Núcleo Celular/metabolismo , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Fundulidae/metabolismo , Frequência do Gene , Genética Populacional , Genótipo , Haplótipos , Desequilíbrio de Ligação , Mitocôndrias/metabolismo , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Fosforilação Oxidativa , Fenótipo , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Delineating the physiological and biochemical causes of aging process in the animal kingdom is a highly active area of research not only because of potential benefits for human health but also because aging process is related to life history strategies (growth and reproduction) and to responses of organisms to environmental conditions and stress. In this synthesis, we advocate studying bivalve species as models for revealing the determinants of species divergences in maximal longevity. This taxonomic group includes the longest living metazoan on earth (Arctica islandica), which insures the widest range of maximum life span when shorter living species are also included in the comparative model. This model can also be useful for uncovering factors modulating the pace of aging in given species by taking advantages of the wide disparity of lifespan among different populations of the same species. For example, maximal lifespan in different populations of A islandica range from approximately 36 years to over 500 years. In the last 15 years, research has revealed that either regulation or tolerance to oxidative stress is tightly correlated to longevity in this group which support further investigations on this taxon to unveil putative mechanistic links between Reactive Oxygen Species and aging process.
Assuntos
Bivalves/metabolismo , Longevidade/genética , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Metabolismo Basal/fisiologia , Bivalves/genética , Bivalves/crescimento & desenvolvimento , Membrana Celular/metabolismo , DNA/genética , DNA/metabolismo , Peroxidação de Lipídeos , Estresse Oxidativo , Reprodução/genéticaRESUMO
Mitochondria produce energy through oxidative phosphorylation (OXPHOS), which depends on the expression of both nuclear and mitochondrial DNA (mtDNA). In metazoans, a striking exception from strictly maternal inheritance of mitochondria is doubly uniparental inheritance (DUI). This unique system involves the maintenance of two highly divergent mtDNAs (F- and M-type, 8-40% of nucleotide divergence) associated with gametes, and occasionally coexisting in somatic tissues. To address whether metabolic differences underlie this condition, we characterized the OXPHOS activity of oocytes, spermatozoa, and gills of different species through respirometry. DUI species express different gender-linked mitochondrial phenotypes in gametes and partly in somatic tissues. The M-phenotype is specific to sperm and entails (i) low coupled/uncoupled respiration rates, (ii) a limitation by the phosphorylation system, and (iii) a null excess capacity of the final oxidases, supporting a strong control over the upstream complexes. To our knowledge, this is the first example of a phenotype resulting from direct selection on sperm mitochondria. This metabolic remodelling suggests an adaptive value of mtDNA variations and we propose that bearing sex-linked mitochondria could assure the energetic requirements of different gametes, potentially linking male-energetic adaptation, mitotype preservation and inheritance, as well as resistance to both heteroplasmy and ageing.
Assuntos
Bivalves/genética , Bivalves/metabolismo , DNA Mitocondrial/genética , Hereditariedade , Fosforilação Oxidativa , Animais , Feminino , Brânquias/metabolismo , Masculino , Oócitos/metabolismo , Espermatozoides/metabolismoRESUMO
Mammalian torpor is a phenotype characterized by a controlled decline of metabolic rate, generally followed by a reduction in body temperature. During arousal from torpor, both metabolic rate and body temperature rapidly returns to resting levels. Metabolic rate reduction experienced by torpid animals is triggered by active suppression of mitochondrial respiration, which is rapidly reversed during rewarming process. In this study, we analyzed the changes in the maximal activity of key enzymes related to electron transport system (complexes I, III and IV) in six tissues of torpid, arousing and euthermic Chilean mouse-opossums (Thylamys elegans). We observed higher maximal activities of complexes I and IV during torpor in brain, heart and liver, the most metabolically active organs in mammals. On the contrary, higher enzymatic activities of complexes III were observed during torpor in kidneys and lungs. Moreover, skeletal muscle was the only tissue without significant differences among stages in all complexes evaluated, suggesting no modulation of oxidative capacities of electron transport system components in this thermogenic tissue. In overall, our data suggest that complexes I and IV activity plays a major role in initiation and maintenance of metabolic suppression during torpor in Chilean mouse-opossum, whereas improvement of oxidative capacities in complex III might be critical to sustain metabolic machinery in organs that remains metabolically active during torpor.
Assuntos
Complexo III da Cadeia de Transporte de Elétrons/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Complexo I de Transporte de Elétrons/metabolismo , Mitocôndrias/metabolismo , Gambás/fisiologia , Fenótipo , Torpor/fisiologia , Animais , Nível de Alerta , Temperatura Corporal , Encéfalo/enzimologia , Transporte de Elétrons , Rim/enzimologia , Fígado/enzimologia , Pulmão/enzimologia , Músculo Esquelético/enzimologia , Miocárdio/enzimologia , OxirreduçãoRESUMO
Refeeding, following a period of food deprivation will often lead to compensatory growth. Although many studies have focused on molecular mechanisms behind this accelerated growth response in fish, little is known on the roles of protein and metabolism. We also assessed, for the first time, the potential roles of miRNAs in regulating compensatory growth. Artcic charr, Salvelinus alpinus, a northern freshwater species, was deprived of food for 101â¯days and then fed to satiety for 126â¯days. The refeeding period resulted in compensatory growth, with a partial compensation of body mass. The feed deprivation period lead to a decrease in hepatosomatic index (HSI) and intestinal somatic index (ISI). HSI and ISI were then gradually replenished during early refeeding, following a lag phase prior to the compensatory growth response. mRNA transcripts regulating protein degradation via the autophagy pathway (Cathepsin D and Cathepsin L) in muscle were upregulated during feed restriction and downregulated after refeeding, which could allow for greater protein accretion in muscle, facilitating compensatory growth. Transcript levels from the ubiquitin proteasome pathway (Mafbx and Murf1) and the calpain system (Calpain 7 and Calpastatin) suggested that these pathways were not involved in regulating compensatory growth. Furthermore, we've shown that miRNAs (miR-29a and miR-223) could be involved in fish glycogen homeostasis during the early stages of refeeding. These findings provide a deeper understanding of the molecular mechanisms regulating growth in fish.
Assuntos
Jejum , Comportamento Alimentar , Glucose/metabolismo , Proteínas/metabolismo , Truta/fisiologia , Animais , Truta/metabolismoRESUMO
Cellular and mitochondrial metabolic capacity of the heart has been suggested to limit performance of fish at warm temperatures. We investigated this hypothesis by studying the effects of acute temperature increases (16, 23, 30, 32.5 and 36°C) on the thermal sensitivity of 10 key enzymes governing cardiac oxidative and glycolytic metabolism in two populations of European perch (Perca fluviatilis) field-acclimated to 15.5 and 22.5°C, as well as the effects of acclimation on cardiac lipid composition. In both populations of perch, the activity of glycolytic (pyruvate kinase and lactate dehydrogenase) and tricarboxylic acid cycle (pyruvate dehydrogenase and citrate synthase) enzymes increased with acute warming. However, at temperatures exceeding 30°C, a drastic thermally induced decline in citrate synthase activity was observed in the cold- and warm-acclimated populations, respectively, indicating a bottleneck for producing the reducing equivalents required for oxidative phosphorylation. Yet, the increase in aspartate aminotransferase and malate dehydrogenase activities occurring in both populations at temperatures exceeding 30°C suggests that the malate-aspartate shuttle may help to maintain cardiac oxidative capacities at high temperatures. Warm acclimation resulted in a reorganization of the lipid profile, a general depression of enzymatic activity and an increased fatty acid metabolism and oxidative capacity. Although these compensatory mechanisms may help to maintain cardiac energy production at high temperatures, the activity of the electron transport system enzymes, such as complexes I and IV, declined at 36°C in both populations, indicating a thermal limit of oxidative phosphorylation capacity in the heart of European perch.
Assuntos
Aclimatação , Aquecimento Global , Mitocôndrias/metabolismo , Percas/fisiologia , Aminoácidos/metabolismo , Animais , Citrato (si)-Sintase/metabolismo , Ciclo do Ácido Cítrico , Ácidos Graxos/análise , Ácidos Graxos/metabolismo , Proteínas de Peixes/metabolismo , Glicólise , Temperatura Alta , Metabolismo dos Lipídeos , Lipídeos/análise , Miocárdio/metabolismo , Oxirredução , TemperaturaRESUMO
Ocean warming and acidification are concomitant global drivers that are currently threatening the survival of marine organisms. How species will respond to these changes depends on their capacity for plastic and adaptive responses. Little is known about the mechanisms that govern plasticity and adaptability or how global changes will influence these relationships across multiple generations. Here, we exposed the emerging model marine polychaete Ophryotrocha labronica to conditions simulating ocean warming and acidification, in isolation and in combination over five generations to identify: (i) how multiple versus single global change drivers alter both juvenile and adult life-history traits; (ii) the mechanistic link between adult physiological and fitness-related life-history traits; and (iii) whether the phenotypic changes observed over multiple generations are of plastic and/or adaptive origin. Two juvenile (developmental rate; survival to sexual maturity) and two adult (average reproductive body size; fecundity) life-history traits were measured in each generation, in addition to three physiological (cellular reactive oxygen species content, mitochondrial density, mitochondrial capacity) traits. We found that multi-generational exposure to warming alone caused an increase in juvenile developmental rate, reactive oxygen species production and mitochondrial density, decreases in average reproductive body size and fecundity, and fluctuations in mitochondrial capacity, relative to control conditions. Exposure to ocean acidification alone had only minor effects on juvenile developmental rate. Remarkably, when both drivers of global change were present, only mitochondrial capacity was significantly affected, suggesting that ocean warming and acidification act as opposing vectors of stress across multiple generations.
Assuntos
Aclimatação , Aquecimento Global , Poliquetos/fisiologia , Ácidos/análise , Animais , Organismos Aquáticos/crescimento & desenvolvimento , Organismos Aquáticos/fisiologia , Evolução Biológica , Tamanho Corporal , Feminino , Fertilidade , Concentração de Íons de Hidrogênio , Masculino , Mitocôndrias/metabolismo , Poliquetos/crescimento & desenvolvimento , Espécies Reativas de Oxigênio/metabolismo , Reprodução , Água do Mar/análiseRESUMO
BACKGROUND: There is increasing evidence that marine omega-3 oils are involved in the reduction of cancer risk and progression. However, the anticancer effect of omega-3 monoglyceride on colorectal cancer has yet to be assessed. The goal of this study was to evaluate the anti-cancer effects of eicosapentaenoic acid monoglyceride (MAG-EPA) in HCT116 colorectal carcinoma cells. METHODS: The effect of MAG-EPA was evaluated in vitro on HCT116 cells and in vivo on mouse model of HCT116 xenograft. RESULTS: Our data reveal that MAG-EPA decreased cell proliferation and induced apoptosis in HCT116 cells. In a xenograft mouse model, daily per os administration of MAG-EPA reduced tumor growth. Furthermore, MAG-EPA treatments decreased EGFR, VEGFR, and AKT activation pathways and reduced VEGF and HIF1α expression levels in tumors. CONCLUSION: MAG-EPA may promote apoptosis and inhibit growth of tumors by suppressing EGFR and VEGFR activation pathways. Altogether, these data provide new evidence regarding the mode of action of MAG-EPA in colorectal cancer cells.
Assuntos
Antineoplásicos/farmacologia , Organismos Aquáticos , Proliferação de Células/efeitos dos fármacos , Ácido Eicosapentaenoico/farmacologia , Células HCT116/efeitos dos fármacos , Monoglicerídeos/farmacologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Animais , Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/parasitologia , Ácido Eicosapentaenoico/uso terapêutico , Feminino , Humanos , Concentração Inibidora 50 , Camundongos , Camundongos Nus , Monoglicerídeos/uso terapêuticoRESUMO
Ulcerative colitis (UC) is a chronic disease characterized by diffuse inflammation of the intestinal mucosa of the large bowel. Omega-3 (ω3) fatty acid supplementation has been associated with a decreased production of inflammatory cytokines involved in UC pathogenesis. The aim of this study was to determine the preventive and therapeutic potential of eicosapentaenoic acid monoglyceride (MAG-EPA) in an in vivo rats model of UC induced by dextran sulfate sodium (DSS). DSS rats were untreated or treated per os with MAG-EPA. Morphological, histological, and biochemical analyses were performed following MAG-EPA administrations. Morphological and histological analyses revealed that MAG-EPA pretreatment (12 days pre-DSS) and treatment (6 days post-DSS) exhibited strong activity in reducing severity of disease in DSS rats. Following MAG-EPA administrations, tissue levels of the proinflammatory cytokines TNF-α, IL-1ß, and IL-6 were markedly lower compared with rats treated only with DSS. MAG-EPA per os administration decrease neutrophil infiltration in colon tissues, as depicted by myelohyperoxidase activity. Results also revealed a reduced activation of NF-κB pathways correlated with a decreased expression of COX-2 in colon homogenates derived from MAG-EPA-pretreated and treated rats. Tension measurements performed on colon tissues revealed that contractile responses to methacholine and relaxing effect induced by sodium nitroprusside were largely increased following MAG-EPA treatment. The combined treatment of MAG-EPA and vitamin E displayed an antagonistic effect on anti-inflammatory properties of MAG-EPA in DSS rats.
Assuntos
Colite Ulcerativa/tratamento farmacológico , Monoglicerídeos/uso terapêutico , Animais , Colite Ulcerativa/etiologia , Colite Ulcerativa/prevenção & controle , Ciclo-Oxigenase 2/metabolismo , Sulfato de Dextrana/toxicidade , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Monoglicerídeos/administração & dosagem , Monoglicerídeos/farmacologia , NF-kappa B/metabolismo , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
The oxidative phosphorylation (OxPhos) pathway is responsible for most aerobic ATP production and is the only metabolic pathway with proteins encoded by both nuclear and mitochondrial genomes. In studies examining mitonuclear interactions among distant populations within a species or across species, the interactions between these two genomes can affect metabolism, growth, and fitness, depending on the environment. However, there is little data on whether these interactions impact natural populations within a single species. In an admixed Fundulus heteroclitus population with northern and southern mitochondrial haplotypes, there are significant differences in allele frequencies associated with mitochondrial haplotype. In this study, we investigate how mitochondrial haplotype and any associated nuclear differences affect six OxPhos parameters within a population. The data demonstrate significant OxPhos functional differences between the two mitochondrial genotypes. These differences are most apparent when individuals are acclimated to high temperatures with the southern mitochondrial genotype having a large acute response and the northern mitochondrial genotype having little, if any acute response. Furthermore, acute temperature effects and the relative contribution of Complex I and II depend on acclimation temperature: when individuals are acclimated to 12°C, the relative contribution of Complex I increases with higher acute temperatures, whereas at 28°C acclimation, the relative contribution of Complex I is unaffected by acute temperature change. These data demonstrate a complex gene by environmental interaction affecting the OxPhos pathway.
Assuntos
Aclimatação/genética , Fundulidae/fisiologia , Interação Gene-Ambiente , Fosforilação Oxidativa , Aclimatação/fisiologia , Alelos , Animais , Peso Corporal , Citocromos c/metabolismo , Complexo I de Transporte de Elétrons/genética , Complexo I de Transporte de Elétrons/metabolismo , Complexo II de Transporte de Elétrons/genética , Complexo II de Transporte de Elétrons/metabolismo , Frequência do Gene , Genótipo , Modelos Lineares , Mitocôndrias/genética , Mitocôndrias/metabolismo , Especificidade da Espécie , TemperaturaRESUMO
ω-3 Fatty acid supplementation has been associated with lower blood pressure. Cardiovascular diseases are also known to be linked directly to an increase in ω-6 and a reduction in ω-3 fatty acid levels in blood circulation and tissues. To determine the effect of docosahexaenoic acid monoglycerides (MAG-DHA) on blood pressure, lipid profiles, and vascular remodeling in rats fed a high-fat/high-carbohydrate (HFHC) diet. Studies were performed in male rats subjected to 8 wk of HFHC diet supplemented or not with 3 g/day MAG-DHA. After 8 wk of daily MAG-DHA treatment, rats in the HFHC + MAG-DHA group had lower arterial blood pressure and heart rate compared with the HFHC group. Moreover, MAG-DHA prevented the increase aortic wall thickness, whereas lipid analysis of aortic tissues revealed an increase in DHA/AA ratio correlated with the production of resolvin D2 and D3 metabolites. Histological analysis revealed that MAG-DHA prevented the development of LVH in the HFHC group. Serum lipid profile analysis further showed a decrease in total cholesterol (TC) and LDL, including very low-density lipoprotein (VLDL) and triglyceride (TG) levels, together with an increase in HDL levels after 8 wk of MAG-DHA treatment compared with the HFHC group. Furthermore, daily MAG-DHA treatment resulted in reduced proinflammatory marker levels such as CRP, IL-6, TNFα, and IL-1ß. Altogether, these findings revealed that per os administration of MAG-DHA prevents HFHC-diet induced hypertension and LVH in rats.
Assuntos
Aorta/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Ventrículos do Coração/efeitos dos fármacos , Hipertensão , Monoglicerídeos/farmacologia , Remodelação Vascular/efeitos dos fármacos , Animais , Aorta/patologia , Proteína C-Reativa/efeitos dos fármacos , Proteína C-Reativa/metabolismo , HDL-Colesterol/efeitos dos fármacos , HDL-Colesterol/metabolismo , LDL-Colesterol/efeitos dos fármacos , LDL-Colesterol/metabolismo , VLDL-Colesterol/efeitos dos fármacos , VLDL-Colesterol/metabolismo , Dieta Hiperlipídica , Ácidos Graxos Ômega-3/farmacologia , Ventrículos do Coração/patologia , Hipertrofia Ventricular Esquerda/patologia , Interleucina-1beta/efeitos dos fármacos , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Ratos , Triglicerídeos/metabolismo , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
n-3 Polyunsaturated fatty acids (n-3 PUFA) have been shown to reduce inflammation and proliferation of pulmonary artery smooth muscle cells under pathophysiological conditions. However, the anti-inflammatory effect of the newly synthesized docosapentaenoic acid monoacylglyceride (MAG-DPA) on key signaling pathways in pulmonary hypertension (PH) pathogenesis has yet to be assessed. The aim of the present study was to determine the effects of MAG-DPA on pulmonary inflammation and remodeling occurring in a rat model of PH, induced by a single injection of monocrotaline (MCT: 60 mg/kg). Our results demonstrate that MAG-DPA treatment for 3 wk following MCT injection resulted in a significant improvement of right ventricular hypertrophy (RVH) and a reduction in Fulton's Index (FI). Morphometric analyses revealed that the wall thickness of pulmonary arterioles was significantly lower in MCT + MAG-DPA-treated rats compared with controls. This result was further correlated with a decrease in Ki-67 immunostaining. Following MAG-DPA treatments, lipid analysis showed a consistent increase in DPA together with lower levels of arachidonic acid (AA), as measured in blood and tissue samples. Furthermore, in MCT-treated rats, oral administration of MAG-DPA decreased NF-κB and p38 MAPK activation, leading to a reduction in MMP-2, MMP-9, and VEGF expression levels in lung tissue homogenates. Altogether, these data provide new evidence regarding the mode of action of MAG-DPA in the prevention of pulmonary hypertension induced by MCT.
Assuntos
Arteríolas/efeitos dos fármacos , Ácidos Graxos Insaturados/uso terapêutico , Hipertensão Pulmonar/tratamento farmacológico , Monoglicerídeos/uso terapêutico , Remodelação Vascular/efeitos dos fármacos , Animais , Ácido Araquidônico/metabolismo , Arteríolas/patologia , Ácidos Graxos Insaturados/farmacologia , Inflamação/tratamento farmacológico , Metabolismo dos Lipídeos , Pulmão/irrigação sanguínea , Pulmão/metabolismo , Masculino , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Monoglicerídeos/farmacologia , NF-kappa B/metabolismo , Ratos , Ratos Wistar , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Mitochondria play a key role in aging. Here, we measured integrated mitochondrial functions in experimentally evolved lines of the seed beetle Acanthoscelides obtectus that were selected for early (E) or late (L) reproduction for nearly four decades. The two lines have markedly different lifespans (8 days and 13 days in the E and L lines, respectively). The contribution of the NADH pathway to maximal flux was lower in the L compared to the E beetles at young stages, associated to increased control by complex I. In contrast, the contribution of the Succinate pathway was higher in the L than in the E line, while the Proline pathway showed no differences between the lines. Our data suggest that selection of age at reproduction leads to a modulation of complex I activity in mitochondria and that mitochondria are a functional link between evolutionary and mechanistic theories of aging.
RESUMO
The aim of this study was to investigate the effect of temperature changes on the functional properties of mitochondria from two sets of D. simulans fly lines harboring the siII and siIII haplotypes in a common nuclear genetic background. We studied four introgressed isofemale lines possessing the mtDNA of siII and the nuclear background of siIII (siII-introgressed) and four lines possessing siIII mitochondria with its native nuclear genome (siIII-controls). We assessed the catalytic capacities of electron transport system (ETS) at four different temperatures (12, 18, 24 and 28 ºC). The impact of temperature on the pyruvate dehydrogenase (PDH) activity, the mitochondrial respiration (coupled and uncoupled respiration), cytochrome c oxidase activity, as well as the excess capacity of complex IV (COX) were evaluated in these two sets of flies. Our results showed that the temperature coefficient values (Q(10)) measured for mitochondrial respiration in the lower range of temperatures (12 to 18 ºC) showed a 2 to 3 fold increase in siII-introgressed when compared to siIII-controls. This result shows that the impact of temperature on mitochondrial function is different between the two mitotypes studied. The Q(10) results seem to be linked to the apparent COX excess capacity of 193% for siIII-controls that is inexistent for siII-introgressed at 12 ºC. One explanation for these results is that the mitochondria can compensate for the disruption of mito-nuclear interactions at 24 ºC but not at lower temperatures. An alternate explanation would be that siII haplotype confer divergent kinetic properties to the ETS that translate to different temperature sensitivities.