PPARs： diverse regulators in energy metabolism and metabolic diseases

The nuclear receptor PPARs are fundamentally important for energy homeostasis. Through their distinct yet overlapping functions and tissue distribution, the PPARs regulate many aspects of energy metabolism at the transcriptional level. Functional impairment or dysregulation of these receptors leads to a variety of metabolic diseases, while their ligands offer many metabolic benefits. Studies of these receptors have advanced our knowledge of the transcriptional basis of energy metabolism and helped us understand the pathogenic mechanisms of metabolic syndrome.

Arginine promotes seed energy metabolism,increasing wheat seed germination at low temperature

Low temperatures during germination inhibit seed growth,lead to small and weak seedlings,and significantly reduce the wheat yield.Alleviating the adverse effects of low temperature on wheat seed germination is highly important for achieving high and stable wheat yields.In this study,Tongmai 6(insensitive)and Zhengmai 113(sensitive),which have different low-temperature sensitivities during germination were treated with low temperature during germination.The transcriptome,metabolome and physiological data revealed that low temperature decreased the germination rate,downregulated the expression of a large number of genes involved in regulating glycometabolism,and inhibited carbon,nitrogen(especially amino acids)and energy metabolism in the seeds.Arginine content increased at low temperature,and its increase in the low-temperature-tolerant variety was significantly greater than that in the sensitive variety.Arginine priming experiment showed that treatment with an appropriate concentration of arginine improved the seed germination rate.The conversion of starch to soluble sugar significantly increased under exogenous arginine conditions,the content of key metabolites in energy metabolism increased,and the utilization of ATP in the seeds increased.Taken together,arginine priming increased seed germination at low temperature by relieving inhibition of seed carbon and nitrogen metabolism and improving seed energy metabolism.

Targeted metabolomics reveals the aberrant energy status in diabetic peripheral neuropathy and the neuroprotective mechanism of traditional Chinese medicine JinMaiTong

Diabetic peripheral neuropathy (DPN) is a common and devastating complication of diabetes, for which effective therapies are currently lacking. Disturbed energy status plays a crucial role in DPN pathogenesis. However, the integrated profile of energy metabolism, especially the central carbohydrate metabolism, remains unclear in DPN. Here, we developed a metabolomics approach by targeting 56 metabolites using high-performance ion chromatography-tandem mass spectrometry (HPIC-MS/MS) to illustrate the integrative characteristics of central carbohydrate metabolism in patients with DPN and streptozotocin-induced DPN rats. Furthermore, JinMaiTong (JMT), a traditional Chinese medicine (TCM) formula, was found to be effective for DPN, improving the peripheral neurological function and alleviating the neuropathology of DPN rats even after demyelination and axonal degeneration. JMT ameliorated DPN by regulating the aberrant energy balance and mitochondrial functions, including excessive glycolysis restoration, tricarboxylic acid cycle improvement, and increased adenosine triphosphate (ATP) generation. Bioenergetic profile was aberrant in cultured rat Schwann cells under high-glucose conditions, which was remarkably corrected by JMT treatment. In-vivo and in-vitro studies revealed that these effects of JMT were mainly attributed to the activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) and downstream peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Our results expand the therapeutic framework for DPN and suggest the integrative modulation of energy metabolism using TCMs, such as JMT, as an effective strategy for its treatment.

Impacts of cold exposure on energy metabolism

Cold stimulation has been shown to regulate glucose,lipid,and amino acid metabolism,while also increasing heat production and energy expenditure in the body.Disordered energy metabolism is a key factor in the onset and progression of chronic metabolic conditiones such as diabetes,obesity,and cardiovascular disease.Recent research has unveiled the myriad pathways through which cold stimulation affects human energy metabolism.This article provides an overview of how cold stimulation affects energy metabolism across the three major metabolic pathways.Furthermore,it explores the implications and potential therapeutic applications of cold stimulation in the prevention and treatment of various metabolic diseases.

Effects of Wuwei Xiaodu Decoction on Uterine Energy Metabolism and Serum Inflammatory Factors in Rats with Acute Pelvic Inflammatory Disease

[Objectives]To observe the effects of Wuwei Xiaodu Decoction on uterine energy metabolism and serum inflammatory factors in the acute pelvic inflammatory disease(APID)model.[Methods]75 Wistar rats(females)were randomly divided into control group,model group and Wuwei Xiaodu Decoction low,medium and high dose groups(n=15).Except for the control group,the rat APID model was established by right uterine inoculation.On the fifth day after inoculation,the low,medium and high dose groups of Wuwei Xiaodu Decoction were administered at 4,8 and 16 g/kg,and the control group and model group received normal saline.Rats were killed 12 h after nondose administration,blood was collected from the abdominal aorta and measured by ELISA for serum interleukin-6(interleukin-6,IL-6),IL-8,and C-reactive proteins(CRP);the right uterus of rats was tested for high-energy phosphate adenosine phosphate(AMP),adenosine diphosphate(ADP),adenosine triphosphate(ATP)and total adenine nucleotides(TAN)level to evaluate the uterine energy metabolism.[Results]AMP,ADP,ATP and TAN were significantly higher in the Wuwei Xiaodu Decoction of low,medium and high dose than the model group,while the serum IL-6,IL-8 and CRP were significantly lower than the model group,and the difference between the low,medium and high doses(P<0.05).[Conclusions]The Wuwei Xiaodu Decoction can dose-dependent promote uterine energy metabolism and inhibit inflammatory response in APID model rats.

Oxidative stress disturbs energy metabolism of mitochondria in ethanol-induced gastric mucosa injury

AIM: To study the role of mitochondrial energy disorder in the pathogenesis of ethanol-induced gastric mucosa injury. METHODS: Wistar rats were used in this study. A gastric mucosal injury model was established by giving the rats alcohol. Gross and microscopic appearance of gastric mucosa and ultrastructure of mitochondria were evaluated. Malondiadehyde (MDA) in gastric mucosa was measured with thiobarbituric acid. Expression of ATP synthase (ATPase) subunits 6 and 8 in mitochondrial DNA (mtDNA) was determined by reverse transcription polymerase chain reaction (RT- PCR). RESULTS:The gastric mucosal lesion index was correlated with the MDA content in gastric mucosa. As the concentration of ethanol was elevated and theexposure time to ethanol was extended, the content of MDA in gastric mucosa increased and the extent of damage aggravated. The ultrastructure of mitochondria was positively related to the ethanol concentration and exposure time. The expression of mtDNA ATPase subunits 6 and 8 mRNA declined with the increasing MDA content in gastric mucosa after gavage with ethanol. CONCLUSION: Ethanol-induced gastric mucosa injury is related to oxidative stress, which disturbs energy metabolism of mitochondria and plays a critical role in the pathogenesis of ethanol-induced gastric mucosa injury.

Cancer metabolic reprogramming: importance, main features, and potentials for precise targeted anti-cancer therapies

Cancer cells are well documented to rewire their metabolism and energy production networks to support and enable rapid proliferation, continuous growth, survival in harsh conditions, invasion, metastasis, and resistance to cancer treatments. Since Dr. Otto Warhurg＇s discovery about altered cancer cell metabolism in 1930, thousands of studies have shed light on various aspects of cancer metabolism with a common goal to find new ways for effectively eliminating tumor cells by targeting their energy metabolism. This review highlights the importance of the main features of cancer metabolism, summarizes recent remarkable advances in this field, and points out the potentials to translate these scientific findings into life-saving diagnosis and therapies to help cancer patients.

Effects of heme oxygenase-1-modified bone marrow mesenchymal stem cells on microcirculation and energy metabolism following liver transplantation

AIM To investigate the effects of heme oxygenase-1(HO-1)-modified bone marrow mesenchymal stem cells(BMMSCs)on the microcirculation and energy metabolism of hepatic sinusoids following reduced-size liver transplantation(RLT)in a rat model.METHODS BMMSCs were isolated and cultured in vitro using an adherent method,and then transduced with HO-1-bearing recombinant adenovirus to construct HO-1/BMMSCs.A rat acute rejection model following 50%RLT was established using a two-cuff technique.Recipients were divided into three groups based on the treatment received:normal saline(NS),BMMSCs and HO-1/BMMSCs.Liver function was examined at six time points.The levels of endothelin-1(ET-1),endothelial nitric-oxide synthase(e NOS),inducible nitric-oxide synthase(i NOS),nitric oxide(NO),and hyaluronic acid(HA)were detected using an enzyme-linked immunosorbent assay.The portal vein pressure(PVP)was detected by Power Lab ML880.The expressions of ET-1,i NOS,e NOS,and von Willebrand factor(v WF)protein in the transplanted liver were detected using immunohistochemistry and Western blotting.ATPase in the transplanted liver was detected by chemical colorimetry,and the ultrastructural changes were observed under a transmission electron microscope.RESULTS HO-1/BMMSCs could alleviate the pathological changes and rejection activity index of the transplanted liver,and improve the liver function of rats following 50%RLT,with statistically significant differences compared with those of the NS group and BMMSCs group(P<0.05).In term of the microcirculation of hepatic sinusoids:The PVP on POD7 decreased significantly in the HO-1/BMMSCs and BMMSCs groups compared with that of the NS group(P<0.01);HO-1/BMMSCs could inhibit the expressions of ET-1 and i NOS,increase the expressions of e NOS and inhibit amounts of NO production,and maintain the equilibrium of ET-1/NO(P<0.05);and HO-1/BMMSCs increased the expression of v WF in hepatic sinusoidal endothelial cells(SECs),and promoted the degradation of HA,compared with those of the NS group and BMMSCs group(P<0.05).In term of the energy metabolism of the transplanted liver,HO-1/BMMSCs repaired the damaged mitochondria,and improved the activity of mitochondrial aspartate aminotransferase(ASTm)and ATPase,compared with the other two groups(P<0.05).CONCLUSION HO-1/BMMSCs can improve the microcirculation of hepatic sinusoids significantly,and recover the energy metabolism of damaged hepatocytes in rats following RLT,thus protecting the transplanted liver.

Wnt gene expression in adult porcine longissimus dorsi and its association with muscle fiber type,energy metabolism,and meat quality

This study investigated the expression profiles of Writ genes in adult porcine Iongissimus dorsi （LD） from different porcine genotypes and their associations with meat quality. The results showed that Wnt5a gene expression level was the highest in Jinhua （JHP） pigs, followed by Zhongbai （ZBP）, DurocxZhongbai （DZB）, and Duroc×Yorkshire×Landrace （DYL） pigs, with significant differences between ZBP, DZB, and DYL （P〈0.05）. This genotypic order was reversed for Wnt7a, Wnt10b, and Wnt11 expression, with JHP and DYL having the lowest and highest expressive levels, respectively. Wnt5a expression was negatively correlated with pH,5 min and ApH （P〈0.01）, some glycolytic markers （P〈0.05）, and positively correlated with meat color （a＊）, shear force （SF） value （P〈0.05）, myosion heavy chain （MyHC） I mRNA proportion （P〈0.01）, turnover ratio of creatine phosphate （CP）, and creatine kinase （CK） activity （P〈0.05）. Opposite correlations were observed for Writ2, Wnt7a, Wnt10b, and Wnt11. These results revealed that Wnt5a, Wnt7a, Wnt10b, and Wnt11 gene expressions in adult porcine muscle contributed to differences between porcine genotypes and affected pork quality. Wnt5a gene expression could be beneficial for the formation of high quality pork by regulating muscle fiber types and postmortem energy metabolism.

Application of methyl jasmonate postharvest maintains the quality of Nanguo pears by regulating mitochondrial energy metabolism

The present study was conducted to investigate the effects of methyl jasmonate(Me JA)dipping treatment on mitochondrial energy metabolism and quality parameters of Nanguo pears during room temperature storage.The results showed that Me JA treatment suppressed the respiration rate and weight loss,and maintained the flesh firmness of Nanguo pears.Me JA also effectively maintained the content of ascorbic acid and titratable acidity in the fruit.Furthermore,the activities of H^(+)-ATPase,Ca^(2+)-ATPase,succinate dehydrogenase(SDH)and cytochrome C oxidase(CCO)of the Me JA-treated fruit were significantly higher than those of the untreated fruit.The contents of adenosine triphosphate(ATP)and adenosine diphosphate(ADP)and the energy charge were also enhanced by Me JA treatment.These results suggest that postharvest Me JA treatment could maintain the quality of Nanguo pears,in part by modulating mitochondrial energy metabolism during room temperature storage.

Resting energy expenditure and glucose, protein and fat oxidation in severe chronic virus hepatitis B patients

AIM: To study and determine the resting energy ex- penditure (REE) and oxidation rates of glucose, fat and protein in severe chronic hepatitis B patients. METHODS: A total of 100 patients with liver diseases were categorized into three groups: 16 in the acute hepatitis group, 56 in the severe chronic hepatitis group, and 28 in the cirrhosis group. The REE and the oxidation rates of glucose, fat and protein were as- sessed by indirect heat measurement using the CCM-D nutritive metabolic investigation system. RESULTS: The REE of the severe chronic hepatitis group (20.7 ± 6.1 kcal/d per kg) was significantly lower than that of the acute hepatitis group (P = 0.014). The respiratory quotient (RQ) of the severe chronic hepatitis group (0.84 ± 0.06) was significantly lower than that of the acute hepatitis and cirrhosis groups (P = 0.001). The glucose oxidation rate of the severe hepatitis group (39.2%) was significantly lower than that of the acute hepatitis group and the cirrhosis group (P < 0.05), while the fat oxidation rate (39.8%) in the severe hepatitis group was markedly higher than that of the other two groups (P < 0.05). With improve- ment of liver function, the glucose oxidation rate in- creased from 41.7% to 60.1%, while the fat oxidation rate decreased from 26.3% to 7.6%. CONCLUSION: The glucose oxidation rate is signifi-cantly decreased, and a high proportion of energy is provided by fat in severe chronic hepatitis. These re- sults warrant a large clinical trail to assess the optimal nutritive support therapy for patients with severe liver disease.

Effects of L-Tetrahydropalmatine on Energy Metabolism,Endothelin-1 and NO during Acute Cerebral Ischemia-reperfusion of Rats

To investigate the effects of L-tetrahydropalmatine (L-THP) on ener-gy metabolism, endothelin-1 (ET-1 ) and NO during acute cerebral ischemia-reperfusion of rats, 24 Wistar rats were randomly divided into four groups, with 6rats in each group: sham-operation group, simple ischemia group, ischemia-reperfusion group and treatment group (L-THP group). Cerebral ATP, lactate,ET-1 and NO levels were measured in all groups. Our results showed that treat-ment with L-THP could increase cerebral ATP levels, but decrease cerebral lac-tate, ET-1 and NO concentrations during ischemia-reperfusion in the treatmentgroup. It is concluded that L-THP could improve cerebral energy metabolism and protect the injured brain tissue, the mechanism of which might be related to suppression of overproduction of ET-1 and NO.

Regulatory effect and mechanisms of carbon monoxidereleasing molecule Ⅱ on hepatic energy metabolism in septic mice

AIM: To investigate the possible mechanisms of exogenous carbon monoxide-releasing molecule II (CORM-2) intervention on hepatic energy metabolism in experimental sepsis.

Metformin improves boar sperm quality via 5′-AMPactivated protein kinase-mediated energy metabolism in vitro

Sperm are specialized cells that require adenosine triphosphate(ATP) to support their function.Maintaining sperm energy homeostasis in vitro is vitally important to improve the efficacy of boar sperm preservation. Metformin can activate 5′-AMPactivated protein kinase(AMPK) to improve metabolic flexibility and maintain energy homeostasis. Thus, the aim of the present study was to investigate whether metformin can improve boar sperm quality through AMPK mediation of energy metabolism. Sperm motility parameters, membrane integrity,acrosomeintegrity,mitochondrial membrane potential(ΔΨm), ATP content, glucose uptake,and lactate efflux were analyzed.Localization and expression levels of AMPK and phospho-Thr172-AMPK(p-AMPK) were also detected by immunofluorescence and western blotting. We found that metformin treatment significantly increased sperm motility parameters, ΔΨm, and ATP content during storage at 17 ℃. Moreover, results showed that AMPK was localized at the acrosomal region, connecting piece, and midpiece of sperm and p-AMPK was distributed at the post-acrosomal region, connecting piece, and midpiece. When sperm were incubated with metformin for 4 h at 37 ℃, sperm motility parameters, ΔΨm, ATP content,p-AMPK, glucose uptake, and lactate efflux all significantly increased, whereas the addition of Compound C treatment, an inhibitor of AMPK,counteracted these positive effects. Together, our results suggest that metformin promotes AMPK activation, which contributes to the maintenance of energy hemostasis and mitochondrial activity,thereby maintaining boar sperm functionality and improving the efficacy of semen preservation.

Natural Products and Derivatives Targeting at Cancer Energy Metabolism:A Potential Treatment Strategy

In the 1920s,Dr Otto Warburg first suggested the significant difference in energy metabolism between malignant cancer cells and adjacent normal cells.Tumor cells mainly adopt the glycolysis as energy source to maintain tumor cell growth and biosynthesis under aerobic conditions.Investigation on energy metabolism pathway in cancer cells has aroused the interest of cancer researchers all around the world.In recent years,plentiful studics suggest that targeting the peculiar cancer energy metabolic pathways,including glycolysis,mitochondrial respiration,amino acid metabolism,and fatty acid oxidation may be an effective strategy to starve cancer cells by blocking essential nutrients.Natural products (NPs)are considered as the “treasure trove of small molecules drugs” and have played an extremely remarkable role in the discovery and development of anticancer drugs.And numerous NPs have been reported to act on cancer energy metabolism targets.Herein,a comprehensive overview about cancer energy metabolism targets and their natural-occurring inhibitors is prepared.

Comprehensive evaluation of the metabolic effects of porcine CRTC3 overexpression on subcutaneous adipocytes with metabolomic and transcriptomic analyses

Background:Meat quality is largely driven by fat deposition,which is regulated by several genes and signaling pathways.The cyclic adenosine monophosphate(cAMP)-regulated transcriptional coactivator 3(CRTC3)is a coactivator of cAMP response element binding protein(CREB)that mediates the function of protein kinase A(PKA)signaling pathway and is involved in various biological processes including lipid and energy metabolism.However,the effects of CRTC3 on the metabolome and transcriptome of porcine subcutaneous adipocytes have not been studied yet.Here,we tested whether porcine CRTC3 expression would be related to fat deposition in Heigai pigs(a local fatty breed in China)and Duroc×Landrace×Yorkshire(DLY,a lean breed)pigs in vivo.The effects of adenovirus-induced CRTC3 overexpression on the metabolomic and transcriptomic profiles of subcutaneous adipocytes were also determined in vitro by performing mass spectrometry-based metabolomics combined with RNA sequencing(RNA-seq).Results:Porcine CRTC3 expression is associated with fat deposition in vivo.In addition,CRTC3 overexpression increased lipid accumulation and the expression of mature adipocyte-related genes in cultured porcine subcutaneous adipocytes.According to the metabolomic analysis,CRTC3 overexpression induced significant changes in adipocyte lipid,amino acid and nucleotide metabolites in vitro.The RNA-seq analysis suggested that CRTC3 overexpression alters the expression of genes and pathways involved in adipogenesis,fatty acid metabolism and glycerophospholipid metabolism in vitro.Conclusions:We identified significant alterations in the metabolite composition and the expression of genes and pathways involved in lipid metabolism in CRTC3-overexpressing adipocytes.Our results suggest that CRTC3 might play an important regulatory role in lipid metabolism and thus affects lipid accumulation in porcine subcutaneous adipocytes.

Effect of Yuxingeng Fluid (愈心梗液) on Myocardial Energy Metabolism in Wistar Rats with Acute Myocardial Infarction

Objective: To examine the effect of Yuxingeng fluid (愈心梗液, YXGF) on myocardial energy metabolism in Wistar rats with acute myocardial infarction (AMI) by observing the ultrastructure of mitochondria and the enzyme activities of rat myocardial adenosine triphosphate (ATP), succinate dehydrogenase (SDH), acid phosphatase (ACP), alkaline phosphatase (ALP) and the content of glycogen. Methods; AMI models were established by ligature of left anterior descending coronary artery and then the rats with AMI were randomly divided into 7 groups: namely, blank group, model group, sham-operated group, captopil group, high-dose YXGF group, middle-dose YXGF group and low-dose YXGF group. From the next day after modeling, the rats were given YXGF through gastrogavage which lasted for 4 weeks. And then, the ultra-structure of mitochondria was observed by electronic microscope and the enzyme activities of ATP, SDH, ACP, ALP and the content of glycogen were determined. Results: Compared with model group, the other three groups of high-dose YXGF, middle-dose YXGF, low-dose YXGF and captopril group could protect the ultrastructure of mitochondria and significantly increase enzyme activities of ATP, SDH, ACP, ALP and the content of glycogen (P<0.01). Conclusion: YXGF can protect mitochondria and increase myocardial enzyme activities and the content of glycogen, which may be one of the mechanisms intervening in the pathological course of the early ventricular remodeling in rats with AMI.

Bone Remodeling and Energy Metabolism:New Perspectives

Bone mineral, adipose tissue and energy metabolism are interconnected by a complex and multilevel series of networks. Calcium and phosphorus are utilized for insulin secretion and synthesis of high energy compounds. Adipose tissue store lipids and cholecalciferol, which, in turn, can influence calcium balance and energy expenditure. Hormones long-thought to solely modulate energy and mineral homeostasis may influence adipocytic function. Osteoblasts are a target of insulin action in bone. Moreover, endocrine mediators, such as osteocalcin, are synthesized in the skeleton but regulate carbohydrate disposal and insulin secretion. Finally, osteoblasts and adipocytes originate from the same mesenchymal progenitor. The mutual crosstalk between osteoblasts and adipocytes within the bone marrow microenvironment plays a crucial role in bone remodeling. In the present review we provide an overview of the reciprocal control between bone and energy metabolism and its clinical implications.

Effect of food restriction on the energy metabolism of the Chinese bulbul（Pycnonotus sinensis）

Food resources play an important role in the regulation of animals’ physiology and behavior. We investigated the effect of short-term food restriction on metabolic thermogenesis of Chinese bulbuls（Pycnonotus sinensis） by measuring changes in body mass, body fat, basic metabolic rate（BMR）, and organ mass of wild-caught Chinese bulbuls from Wenzhou, China. Short-term food restriction induced a significant decrease in body mass and body fat but body mass returned to normal levels soon after food was no longer restricted. Food restriction caused a significant reduction in BMR after 7 days（P〈0.05）, which returned to normal levels after food restriction ceased. Log total BMR was positively correlated with log body mass（r2=0.126, P〈0.05）. The dry masses of livers and the digestive tract were higher in birds that had been subject to temporary food restriction than in control birds and those subject to continual food restriction（P〈0.001 and P〈0.05, respectively）. There was also significant differences in the dry mass of the lungs（P〈0.05）, heart（P〈0.01）, and spleen（P〈0.05） in birds subject to short-term food restriction compared to control birds and those subject to continual food restriction. BMR was positively correlated with body and organ（heart, kidney and stomach） mass. These results suggest that the Chinese bulbul adjusts to restricted food availability by utilizing its energy reserves, lowering its BMR and changing the weight of various internal organs so as to balance total energy requirements. These may all be survival strategies that allow birds to cope with unpredictable variation in food abundance.

Energy status regulated umami compound metabolism in harvested shiitake mushrooms(Lentinus edodes)with spores triggered to release

The molecular mechanisms of energy status related to the umami taste of postharvest shiitake mushrooms during spore release remain poorly understood.In this study,the variations of energy status and umami taste of mushrooms were measured at 25℃.At 24 h storage,slight spore prints of mushrooms were first pictured,respiration peaked.Significant ATP decrease and ADP increase were also observed as the initiation of postharvest senescence(P<0.05).Meanwhile,the activities of phosphohexose isomerase,succinate dehydrogenase,glucose-6-phosphate dehydrogenase and cytochrome c oxidase and the contents of umami nucleotides and amino acids were maintained at higher levels in mushrooms with spore release.Notably,the equivalent umami concentration(EUC)was strongly correlated with energy levels(R=0.80).Fifteen related gene expression levels in the energy metabolism pathway were downregulated.LecpdP1 and LeAK were significantly expressed in the conversion of ATP into AMP and played key roles in connecting the energy state and umami level.These results provided valuable insights on the umami taste associated with energy metabolism mechanism during postharvest mushroom spore release.