Proteome analysis of fatty liver in feed-deprived dairy cows reveals interaction of fuel sensing, calcium, fatty acid, and glycogen metabolism

2009 ◽  
Vol 37 (2) ◽  
pp. 88-98 ◽  
Author(s):  
Björn Kuhla ◽  
Dirk Albrecht ◽  
Siegfried Kuhla ◽  
Cornelia C. Metges
Keyword(s):  
Fatty Acid ◽  
Dairy Cows ◽  
Antigen Processing ◽  
Energy Homeostasis ◽  
Liver Fat ◽  
Oxidative Enzymes ◽  
Metabolic Adaptation ◽  
Acid Oxidation ◽  
Total Liver ◽  
Feed Deprivation

The liver of dairy cows is involved in signaling the current hepatic metabolic state to the brain via metabolites and nerval afferents to control and adjust feed intake. Feed deprivation may result in mobilization of body reserves favoring hepatic steatosis. While the overall metabolic changes are well characterized, specific regulatory mechanisms are not readily understood. To identify molecular events associated with metabolic adaptation and the control of energy homeostasis, liver specimens from six ad libitum-fed and six feed-deprived cows were analyzed for selected metabolites, for the activation of AMP kinase, and for regulatory/regulated proteins using two-dimensional gel electrophoresis and MALDI-TOF-MS. Feed deprivation increased total liver fat and the calcium content, as well as augmented AMPK phosphorylation, while it decreased the contents of protein, glucose, glycogen, and cholesterol when expressed as a percentage of dry matter. Among 34 differentially expressed proteins identified, we found downregulation of proteins associated with fatty acid oxidation, glycolysis, electron transfer, protein degradation, and antigen processing, as well as cytoskeletal rearrangement. Proteins upregulated after feed deprivation included enzymes of the urea cycle, fatty acid or cholesterol transport proteins, an inhibitor of glycolysis, and previously unknown changes in calcium signaling network. Direct correlation was found between expression of glycolytic enzymes and glucose/glycogen content, whereas inverse correlation exists between expression of β-oxidative enzymes and total liver fat content. In conclusion, the regulatory response of identified proteins may help to explain development and consequences of hepatic lipidosis but also offers novel candidates potentially involved in signaling for maintaining energy homeostasis.

scholarly journals AMPK as a mediator of hormonal signalling

2009 ◽  
Vol 44 (2) ◽  
pp. 87-97 ◽  
Author(s):  
Chung Thong Lim ◽  
Blerina Kola ◽  
Márta Korbonits
Keyword(s):  
Protein Synthesis ◽  
Fatty Acid ◽  
Metabolic Disorders ◽  
Energy Homeostasis ◽  
Metabolic Effects ◽  
Whole Body ◽  
Acid Oxidation ◽  
Treatment Of Obesity ◽  
Amp Activated Protein Kinase ◽  
Hormonal Signalling

AMP-activated protein kinase (AMPK) is a key molecular player in energy homeostasis at both cellular and whole-body levels. AMPK has been shown to mediate the metabolic effects of hormones such as leptin, ghrelin, adiponectin, glucocorticoids and insulin as well as cannabinoids. Generally, activated AMPK stimulates catabolic pathways (glycolysis, fatty acid oxidation and mitochondrial biogenesis) and inhibits anabolic pathways (gluconeogenesis, glycogen, fatty acid and protein synthesis), and has a direct appetite-regulating effect in the hypothalamus. Drugs that activate AMPK, namely metformin and thiazolidinediones, are often used to treat metabolic disorders. Thus, AMPK is now recognised as a potential target for the treatment of obesity and associated co-morbidities.

scholarly journals IL-15Rα is a determinant of muscle fuel utilization, and its loss protects against obesity

2015 ◽  
Vol 309 (8) ◽  
pp. R835-R844 ◽  
Author(s):  
Emanuele Loro ◽  
Erin L. Seifert ◽  
Cynthia Moffat ◽  
Freddy Romero ◽  
Manoj K. Mishra ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Energy Homeostasis ◽  
Wide Distribution ◽  
Liver Fat ◽  
Acid Oxidation ◽  
Direct Effects ◽  
High Fat ◽  
Binding Partner ◽  
Insulin Resistant ◽  
Diet Induced Obesity

IL-15Rα is the widely expressed primary binding partner for IL-15. Because of the wide distribution in nonlymphoid tissues like skeletal muscle, adipose, or liver, IL-15/IL-15Rα take part in physiological and metabolic processes not directly related to immunity. In fast muscle, lack of IL-15Rα promotes an oxidative switch, with increased mitochondrial biogenesis and fatigue resistance. These effects are predicted to reproduce some of the benefits of exercise and, therefore, improve energy homeostasis. However, the direct effects of IL-15Rα on metabolism and obesity are currently unknown. We report that mice lacking IL-15Rα (IL-15Rα−/−) are resistant to diet-induced obesity (DIO). High-fat diet-fed IL-15Rα−/− mice have less body and liver fat accumulation than controls. The leaner phenotype is associated with increased energy expenditure and enhanced fatty acid oxidation by muscle mitochondria. Despite being protected against DIO, IL-15Rα−/− are hyperglycemic and insulin-resistant. These findings identify novel roles for IL-15Rα in metabolism and obesity.

Proteomic analysis of the effects of lutein on mammary gland metabolism in dairy cows

2018 ◽  
Vol 85 (2) ◽  
pp. 152-156
Author(s):  
Caihong Wang ◽  
Chong Wang ◽  
Jianxin Liu ◽  
Hongyun Liu
Keyword(s):  
Blood Flow ◽  
Mammary Gland ◽  
Fatty Acid ◽  
Dairy Cows ◽  
Control Diet ◽  
Differentially Expressed ◽  
Acid Oxidation ◽  
Differentially Expressed Proteins ◽  
Proteomic Approach ◽  
Increased Blood Flow

The aim of the research reported in this Research Communication was to identify differentially expressed proteins in dairy cows with normal and lutein diet and to elucidate the mechanisms of lutein-induced effects on bovine mammary gland metabolism using a comparative proteomic approach. Thirty-three differentially expressed proteins were identified from mammary gland of control diet-fed and lutein diet-fed dairy cows. Among these proteins, 15 were upregulated and 18 were downregulated in the lutein group. Functional analysis of the differentially expressed proteins showed that increased blood flow, depressed glycolysis, enhanced lactose anabolism, decreased fatty acid oxidation and up-regulated beta lactoglobulin expression were connected with lutein addition. These results suggested that the increased blood flow, reduced glucose catabolism, enhanced capacity for milk lactose synthesis, depressed fatty acid catabolism and increased expression of antioxidantion related protein may be the prime factors contributing to the increased milk production and enhanced immune status in lutein-fed dairy cows. This study provides molecular mechanism of dietary lutein in regulating lactation of dairy cows.

Improved energy homeostasis of the heart in the metabolic state of exercise

2000 ◽  
Vol 279 (4) ◽  
pp. H1490-H1501 ◽  
Author(s):  
Gary W. Goodwin ◽  
Heinrich Taegtmeyer ◽  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Energy Homeostasis ◽  
Acid Oxidation ◽  
High Fat ◽  
Nonesterified Fatty Acids ◽  
Malonyl Coa ◽  
Metabolic Conditions ◽  
High Lactate

We postulate that metabolic conditions that develop systemically during exercise (high blood lactate and high nonesterified fatty acids) are favorable for energy homeostasis of the heart during contractile stimulation. We used working rat hearts perfused at physiological workload and levels of the major energy substrates and compared the metabolic and contractile responses to an acute low-to-high work transition under resting versus exercising systemic metabolic conditions (low vs. high lactate and nonesterified fatty acids in the perfusate). Glycogen preservation, resulting from better maintenance of high-energy phosphates, was a consequence of improved energy homeostasis with high fat and lactate. We explained the result by tighter coupling between workload and total β-oxidation. Total fatty acid oxidation with high fat and lactate reflected increased availability of exogenous and endogenous fats for respiration, as evidenced by increased long-chain fatty acyl-CoA esters (LCFA-CoAs) and by an increased contribution of triglycerides to total β-oxidation. Triglyceride turnover (synthesis and degradation) also appeared to increase. Elevated LCFA-CoAs caused high total β-oxidation despite increased malonyl-CoA. The resulting bottleneck at mitochondrial uptake of LCFA-CoAs stimulated triglyceride synthesis. Our results suggest the following. First, both malonyl-CoA and LCFA-CoAs determine total fatty acid oxidation in heart. Second, concomitant stimulation of peripheral glycolysis and lipolysis should improve cardiac energy homeostasis during exercise. We speculate that high lactate contributes to the salutary effect by bypassing the glycolytic block imposed by fatty acids, acting as an anaplerotic substrate necessary for high tricarbocylic acid cycle flux from fatty acid-derived acetyl-CoA.

scholarly journals Regulation of Fatty Acid Oxidation by Twist 1 in the Metabolic Adaptation of T Helper Lymphocytes to Chronic Inflammation

2019 ◽  
Vol 71 (10) ◽  
pp. 1756-1765 ◽  
Author(s):  
Kristyna Hradilkova ◽  
Patrick Maschmeyer ◽  
Kerstin Westendorf ◽  
Heidi Schliemann ◽  
Olena Husak ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Chronic Inflammation ◽  
Fatty Acid Oxidation ◽  
Metabolic Adaptation ◽  
Acid Oxidation ◽  
T Helper ◽  
T Helper Lymphocytes ◽  
Twist 1

Site of action of putative lipostatic factor: hypothalamic metabolism of parabiotic rats

1989 ◽  
Vol 257 (1) ◽  
pp. R224-R228
Author(s):  
T. R. Kasser ◽  
R. B. Harris ◽  
R. J. Martin
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Caloric Intake ◽  
Metabolic Adaptation ◽  
Acid Oxidation ◽  
Gamma Aminobutyric Acid ◽  
Glucose Flux ◽  
Site Of Action ◽  
Net Flux ◽  
Ad Libitum

Studies were conducted to determine whether metabolic adaptation occurred in the hypothalamus of overfed parabiotic rats and their partners to distinguish between the adaptations caused by increased caloric intake and those caused by the production of a "lipostatic factor." The induction of overfed obesity in one parabiotic partner was employed to test the hypothesis that a putative lipostatic factor produced in the obese parabiotic elicited the hypophagic-lipid-mobilizing effect observed in the lean parabiotic via alterations in hypothalamic fatty acid and glucose metabolism. Fatty acid oxidation in the ventrolateral hypothalamus (VLH) of overfed parabiotic rats and their partners was lower than in ad libitum parabiotic rats. Net flux of glucose through the VLH gamma-aminobutyric acid (GABA) shunt was elevated in overfed parabiotic rats compared with the net flux observed in their partners and ad libitum parabiotic rats, the levels being similar in these last two groups. Net flux of glucose through the ventromedial hypothalamic (VMH) pentose shunt in overfed parabiotic rats and their partners was elevated relative to ad libitum parabiotic rats. The putative lipostatic factor may act to regulate energy balance through modification of VLH fatty acid oxidation and/or glucose flux via the VMH pentose shunt.

scholarly journals TXNIP regulates myocardial fatty acid oxidation via miR-33a signaling

2016 ◽  
Vol 311 (1) ◽  
pp. H64-H75 ◽  
Author(s):  
Junqin Chen ◽  
Martin E. Young ◽  
John C. Chatham ◽  
David K. Crossman ◽  
Louis J. Dell'Italia ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Energy Homeostasis ◽  
Target Genes ◽  
Contractile Function ◽  
Regulatory Element ◽  
Cardiac Metabolism ◽  
Acid Oxidation ◽  
Myocardial Fatty Acid ◽  
Human Cardiomyocytes ◽  
Perfusion Studies

Myocardial fatty acid β-oxidation is critical for the maintenance of energy homeostasis and contractile function in the heart, but its regulation is still not fully understood. While thioredoxin-interacting protein (TXNIP) has recently been implicated in cardiac metabolism and mitochondrial function, its effects on β-oxidation have remained unexplored. Using a new cardiomyocyte-specific TXNIP knockout mouse and working heart perfusion studies, as well as loss- and gain-of-function experiments in rat H9C2 and human AC16 cardiomyocytes, we discovered that TXNIP deficiency promotes myocardial β-oxidation via signaling through a specific microRNA, miR-33a. TXNIP deficiency leads to increased binding of nuclear factor Y (NFYA) to the sterol regulatory element binding protein 2 (SREBP2) promoter, resulting in transcriptional inhibition of SREBP2 and its intronic miR-33a. This allows for increased translation of the miR-33a target genes and β-oxidation-promoting enzymes, carnitine octanoyl transferase (CROT), carnitine palmitoyl transferase 1 (CPT1), hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase-β (HADHB), and AMPKα and is associated with an increase in phospho-AMPKα and phosphorylation/inactivation of acetyl-CoA-carboxylase. Thus, we have identified a novel TXNIP-NFYA-SREBP2/miR-33a-AMPKα/CROT/CPT1/HADHB pathway that is conserved in mouse, rat, and human cardiomyocytes and regulates myocardial β-oxidation.

scholarly journals Dietary fat sensing via fatty acid oxidation in enterocytes: possible role in the control of eating

2011 ◽  
Vol 300 (3) ◽  
pp. R554-R565 ◽  
Author(s):  
Wolfgang Langhans ◽  
Claudia Leitner ◽  
Myrtha Arnold
Keyword(s):  
Fatty Acids ◽  
Small Intestine ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Energy Homeostasis ◽  
Vagal Afferents ◽  
Acid Oxidation ◽  
Physiological Relevance ◽  
Vagal Afferent ◽  
Afferent Signaling

Various mechanisms detect the presence of dietary triacylglycerols (TAG) in the digestive tract and link TAG ingestion to the regulation of energy homeostasis. We here propose a novel sensing mechanism with the potential to encode dietary TAG-derived energy by translating enterocyte fatty acid oxidation (FAO) into vagal afferent signals controlling eating. Peripheral FAO has long been implicated in the control of eating ( 141 ). The prevailing view was that mercaptoacetate (MA) and other FAO inhibitors stimulate eating by modulating vagal afferent signaling from the liver. This concept has been challenged because hepatic parenchymal vagal afferent innervation is scarce and because experimentally induced changes in hepatic FAO often fail to affect eating. Nevertheless, intraperitoneally administered MA acts in the abdomen to stimulate eating because this effect was blocked by subdiaphragmatic vagal deafferentation ( 21 ), a surgical technique that eliminates all vagal afferents from the upper gut. These and other data support a role of the small intestine rather than the liver as a FAO sensor that can influence eating. After intrajejunal infusions, MA also stimulated eating in rats through vagal afferent signaling, and after infusion into the superior mesenteric artery, MA increased the activity of celiac vagal afferent fibers originating in the proximal small intestine. Also, pharmacological interference with TAG synthesis targeting the small intestine induced a metabolic profile indicative of increased FAO and inhibited eating in rats on a high-fat diet but not on chow. Finally, cell culture studies indicate that enterocytes oxidize fatty acids, which can be modified pharmacologically. Thus enterocytes may sense dietary TAG-derived fatty acids via FAO and influence eating through changes in intestinal vagal afferent activity. Further studies are necessary to identify the link between enterocyte FAO and vagal afferents and to examine the specificity and potential physiological relevance of such a mechanism.

scholarly journals Effect of inhibition of fatty acid oxidation on neonatal liver carnitine content

1982 ◽  
Vol 204 (3) ◽  
pp. 861-863 ◽  
Author(s):  
Susan C. Frost ◽  
Michael A. Wells
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Inhibitory Effect ◽  
Free Carnitine ◽  
Acid Oxidation ◽  
Total Liver ◽  
Hypoglycaemic Agent ◽  
Neonatal Liver ◽  
Acid Compound

The hypoglycaemic agent 2-tetradecylglycidic acid (compound McN-3802) caused an increase in total liver carnitine content, this being due primarily to an increase in the free carnitine pool. In the neonatal animal, this may represent a mechanism to overcome the inhibitory effect of fatty acid oxidation by the drug.

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