Increased 4-enoyl-CoA reductase activity in liver mitochondria of rats fed high-fat diets and its effect on fatty acid oxidation and the inhibitory action of pent-4-enoate

Fatty acid oxidation and synthesis were studied in isolated hepatocytes from adult rats adapted for 44 days on low-fat, high-carbohydrate (LF), diet or high-fat diets, composed of long-chain (LCT) or medium-chain (MCT) triacylglycerols. The rates of [1-14C]octanoate oxidation were almost similar in each group studied, whereas the oxidation of [1-14C]oleate was 50% lower in the LF group than in animals adapted to high-fat diets. The rates of oleate oxidation are inversely correlated with the rates of lipogenesis. However, it seems unlikely that [malonyl-CoA] itself represents the sole mechanism involved in the regulation of oleate oxidation during long-term LCT or MCT feeding, since: (1) despite a 3-fold higher concentration of malonyl-CoA in MCT-fed rats than in LCT-fed ones, the rates of oleate oxidation are similar; (2) when malonyl-CoA concentration is increased after stimulation of lipogenesis (by adding lactate + pyruvate) in MCT-fed rats, to a level comparable with that of the LF group, the rate of oleate oxidation remains 55% higher than that measured under similar conditions in the LF-fed rats; (3) in the LF group, the 90% decrease in malonyl-CoA concentration [by 5-(tetradecyloxy)-2-furoic acid] is not associated with a stimulation of oleate oxidation. By contrast, the sensitivity of carnitine palmitoyltransferase I (CPT I) to malonyl-CoA is markedly decreased in the LCT- and MCT-fed rats, by 90% and 70% respectively. The relevance of this decrease in the sensitivity of CPT I is discussed.

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Abstract 437: Increasing Cardiac Fatty Acid Oxidation Protects Against High Fat Diet Induced Cardiomyopathy in Mice

Circulation Research ◽

10.1161/res.119.suppl_1.437 ◽

2016 ◽

Vol 119 (suppl_1) ◽

Author(s):

Dan Shao ◽

Nathan Roe ◽

Loreta D Tomasi ◽

Alyssa N Braun ◽

Ana Mattos ◽

...

Keyword(s):

Fatty Acid ◽

Fatty Acid Oxidation ◽

Cardiac Dysfunction ◽

High Fat Diet ◽

Heart Weight ◽

Acid Oxidation ◽

Acid Uptake ◽

High Fat ◽

Diet Induced Obesity ◽

Cardiac Lipotoxicity

In the obese and diabetic heart, an imbalance between fatty acid uptake and fatty acid oxidation (FAO) promotes the development of cardiac lipotoxicity. We previously showed that cardiac specific deletion of acetyl CoA carboxylase 2 (ACC2) was effective in increasing myocardial FAO while maintaining normal cardiac function and energetics. In this study, we tested the hypothesis that ACC2 deletion in an adult heart would prevent the cardiac lipotoxic phenotype in a mouse model of diet-induced obesity. ACC2 flox/flox (CON) and ACC2 flox/flox-MerCreMer+ (iKO) after tamoxifen injection were subjected to a high fat diet (HFD) for 24 weeks. HFD induced similar body weight gain and glucose intolerance in CON and iKO. In isolated Langendorff-perfused heart experiments, HFD feeding increased FAO 1.6-fold in CON mice which was increased to 2.5-fold in iKO mice compared with CON on chow diet. Fractional shortening was significantly decreased in CON-HFD (32.8±2.8% vs. 39.2±3.2%, p< 0.05, n=5-6), but preserved in iKO-HFD mice (42.8±2.3%, vs. 38.5±1.4%, n=6), compared to respective chow fed controls. Diastolic function, assessed by E’/A’ ratio using tissue Doppler imaging, was significantly decreased in CON-HFD mice (1.11±0.08 vs. 0.91±0.09, p<0.05 n=5-6), while no difference was observed in iKO-HFD compared to iKO-chow (1.10±0.03 vs. 1.09±0.04, n=6). Heart weight /Tibia length ratio was significantly higher in CON than iKO mice after HFD feeding (7.19±0.22 vs. 6.47±0.28, p<0.05, n=6). Furthermore, HFD induced mitochondria super complex II, III and V instability, which was attenuated in iKO-HFD mice. These data indicate that elevated myocardial FAO per se does not cause the development of cardiac dysfunction in obese animals. In fact, enhancing FAO via ACC2 deletion prevents HFD induced cardiac dysfunction and attenuates pathological hypertrophy. These effects may be mediated, in part, by maintenance of mitochondrial integrity. Taken together, our findings suggest that promoting cardiac FAO is an effective strategy to resist the development of cardiac lipotoxicity during diet-induced obesity.

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Abstract 282: Increasing Cardiac Fatty Acid Oxidation Protects Against High Fat Diet Induced Mitochondria Dysfunction and Cardiomyopathy in Mice

Circulation Research ◽

10.1161/res.123.suppl_1.282 ◽

2018 ◽

Vol 123 (Suppl_1) ◽

Cited By ~ 1

Author(s):

Dan Shao ◽

Stephen C. Kolwicz ◽

Nathan Roe ◽

Outi Villet ◽

Rong Tian

Keyword(s):

Fatty Acid ◽

Fatty Acid Oxidation ◽

High Fat Diet ◽

Acid Oxidation ◽

High Fat ◽

Mitochondria Dysfunction

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Proteomics study of the effect of high-fat diet on rat liver

British Journal Of Nutrition ◽

10.1017/s0007114519001740 ◽

2019 ◽

Vol 122 (9) ◽

pp. 1062-1072 ◽

Cited By ~ 1

Author(s):

Jian Sang ◽

Hengxian Qu ◽

Ruixia Gu ◽

Dawei Chen ◽

Xia Chen ◽

...

Keyword(s):

Fatty Acid ◽

Rat Liver ◽

High Fat Diet ◽

Acid Synthesis ◽

High Energy ◽

The Body ◽

Acid Oxidation ◽

High Fat ◽

Bioinformatics Analyses ◽

Fat Diets

AbstractExcessive intake of high-energy diets is an important cause of most obesity. The intervention of rats with high-fat diet can replicate the ideal animal model for studying the occurrence of human nutritional obesity. Proteomics and bioinformatics analyses can help us to systematically and comprehensively study the effect of high-fat diet on rat liver. In the present study, 4056 proteins were identified in rat liver by using tandem mass tag. A total of 198 proteins were significantly changed, of which 103 were significantly up-regulated and ninety-five were significantly down-regulated. These significant differentially expressed proteins are primarily involved in lipid metabolism and glucose metabolism processes. The intake of a high-fat diet forces the body to maintain physiological balance by regulating these key protein spots to inhibit fatty acid synthesis, promote fatty acid oxidation and accelerate fatty acid degradation. The present study enriches our understanding of metabolic disorders induced by high-fat diets at the protein level.

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

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.2000.279.4.h1490 ◽

2000 ◽

Vol 279 (4) ◽

pp. H1490-H1501 ◽

Cited By ~ 73

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.

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Effects of 2-mercaptoacetate in isolated liver mitochondria in vitro. Competitive inhibition of 3-hydroxybutyrate dehydrogenase and depression of the β-oxidation pathway

Biochemical Journal ◽

10.1042/bj2060053 ◽

1982 ◽

Vol 206 (1) ◽

pp. 53-59 ◽

Cited By ~ 15

Author(s):

F Bauché ◽

D Sabourault ◽

Y Giudicelli ◽

J Nordmann ◽

R Nordmann

Keyword(s):

Fatty Acid ◽

Fatty Acid Oxidation ◽

Competitive Inhibition ◽

Liver Mitochondria ◽

Inhibitory Effect ◽

Acid Oxidation ◽

Membrane Bound ◽

Energy Dependent ◽

Isolated Liver

The effects of 2-mercaptoacetate on the respiration rates induced by different substrates were studied in vitro in isolated liver mitochondria. With palmitoyl-L-carnitine or 2-oxoglutarate as the substrate, the ADP-stimulated respiration (State 3) was dose-dependently inhibited by 2-mercaptoacetate. with glutamate or succinate as the substrate. State-3 respiration was only slightly inhibited by 2-mercaptoacetate. In contrast, the oxidation rate of 3-hydroxybutyrate was competitively inhibited by 2-mercaptoacetate in both isolated mitochondria and submitochondrial particles. In uncoupled mitochondria and in mitochondria in which ATP- and GTP-dependent acyl-CoA biosynthesis was inhibited, the inhibitory effect of 2-mercaptoacetate on palmitoyl-L-carnitine oxidation was abolished; under the same conditions, however, inhibition of 3-hydroxybutyrate oxidation by 2-mercaptoacetate still persisted. These results led to the following conclusions: 2-mercaptoacetate itself enters the mitochondrial matrix, inhibits fatty acid oxidation through a mechanism requiring an energy-dependent activation of 2-mercaptoacetate and itself inhibits 3-hydroxybutyrate oxidation through a competitive inhibition of the membrane-bound 3-hydroxybutyrate dehydrogenase. This study also strongly suggests that the compound responsible for the inhibition of fatty acid oxidation is 2-mercaptoacetyl-CoA.

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Peroxisome Proliferator-Activated Receptor α Mediates the Effects of High-Fat Diet on Hepatic Gene Expression

Endocrinology ◽

10.1210/en.2005-1132 ◽

2006 ◽

Vol 147 (3) ◽

pp. 1508-1516 ◽

Cited By ~ 194

Author(s):

David Patsouris ◽

Janardan K. Reddy ◽

Michael Müller ◽

Sander Kersten

Keyword(s):

Fatty Acid ◽

Fatty Acid Oxidation ◽

Microarray Analysis ◽

High Fat Diet ◽

Acid Oxidation ◽

Peroxisome Proliferator ◽

Dependent Manner ◽

Wild Type ◽

High Fat ◽

Fat Feeding

Peroxisome proliferator-activated receptors (PPARs) are transcription factors involved in the regulation of numerous metabolic processes. The PPARα isotype is abundant in liver and activated by fasting. However, it is not very clear what other nutritional conditions activate PPARα. To examine whether PPARα mediates the effects of chronic high-fat feeding, wild-type and PPARα null mice were fed a low-fat diet (LFD) or high-fat diet (HFD) for 26 wk. HFD and PPARα deletion independently increased liver triglycerides. Furthermore, in wild-type mice HFD was associated with a significant increase in hepatic PPARα mRNA and plasma free fatty acids, leading to a PPARα-dependent increase in expression of PPARα marker genes CYP4A10 and CYP4A14. Microarray analysis revealed that HFD increased hepatic expression of characteristic PPARα target genes involved in fatty acid oxidation in a PPARα-dependent manner, although to a lesser extent than fasting or Wy14643. Microarray analysis also indicated functional compensation for PPARα in PPARα null mice. Remarkably, in PPARα null mice on HFD, PPARγ mRNA was 20-fold elevated compared with wild-type mice fed a LFD, reaching expression levels of PPARα in normal mice. Adenoviral overexpression of PPARγ in liver indicated that PPARγ can up-regulate genes involved in lipo/adipogenesis but also characteristic PPARα targets involved in fatty acid oxidation. It is concluded that 1) PPARα and PPARα-signaling are activated in liver by chronic high-fat feeding; and 2) PPARγ may compensate for PPARα in PPARα null mice on HFD.

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RS4-type resistant starch prevents high-fat diet-induced obesity via increased hepatic fatty acid oxidation and decreased postprandial GIP in C57BL/6J mice

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00468.2009 ◽

2010 ◽

Vol 298 (3) ◽

pp. E652-E662 ◽

Cited By ~ 41

Author(s):

Akira Shimotoyodome ◽

Junko Suzuki ◽

Daisuke Fukuoka ◽

Ichiro Tokimitsu ◽

Tadashi Hase

Keyword(s):

Fatty Acid ◽

Fatty Acid Oxidation ◽

Resistant Starch ◽

High Fat Diet ◽

Acid Oxidation ◽

High Fat ◽

Fat Utilization ◽

Hepatic Fatty Acid ◽

Diet Induced Obesity ◽

Hepatic Fatty Acid Oxidation

Chemically modified starches (CMS) are RS4-type resistant starch, which shows a reduced availability, as well as high-amylose corn starch (HACS, RS2 type), compared with the corresponding unmodified starch. Previous studies have shown that RS4 increases fecal excretion of bile acids and reduces zinc and iron absorption in rats. The aim of this study was to investigate the effects of dietary RS4 supplementation on the development of diet-induced obesity in mice. Weight- and age-matched male C57BL/6J mice were fed for 24 wk on a high-fat diet containing unmodified starch, hydroxypropylated distarch phosphate (RS4), or HACS (RS2). Those fed the RS4 diet had significantly lower body weight and visceral fat weight than those fed either unmodified starch or the RS2 diet. Those fed the RS4 diet for 4 wk had a significantly higher hepatic fatty acid oxidation capacity and related gene expression and lower blood insulin than those fed either unmodified starch or the RS2 diet. Indirect calorimetry showed that the RS4 group exhibited higher energy expenditure and fat utilization compared with the RS2 group. When gavaged with fat (trioleate), RS4 stimulated a lower postprandial glucose-dependent insulinotropic polypeptide (GIP; incretin) response than RS2. Higher blood GIP levels induced by chronic GIP administration reduced fat utilization in high-fat diet-fed mice. In conclusion, dietary supplementation with RS4-type resistant starch attenuates high-fat diet-induced obesity more effectively than RS2 in C57BL/6J mice, which may be attributable to lower postprandial GIP and increased fat catabolism in the liver.

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Correction: Black bean protein concentrate ameliorates hepatic steatosis by decreasing lipogenesis and increasing fatty acid oxidation in rats fed a high fat-sucrose diet

Food & Function ◽

10.1039/d0fo90059a ◽

2021 ◽

Author(s):

Irma Hernandez-Velazquez ◽

Monica Sanchez-Tapia ◽

Guillermo Ordaz-Nava ◽

Nimbe Torres ◽

Armando R. Tovar ◽

...

Keyword(s):

Fatty Acid ◽

Hepatic Steatosis ◽

Fatty Acid Oxidation ◽

Acid Oxidation ◽

Protein Concentrate ◽

High Fat ◽

Black Bean ◽

Sucrose Diet ◽

Bean Protein

Correction for ‘Black bean protein concentrate ameliorates hepatic steatosis by decreasing lipogenesis and increasing fatty acid oxidation in rats fed a high fat-sucrose diet’ by Irma Hernandez-Velazquez et al., Food Funct., 2020, DOI: 10.1039/d0fo02258f.

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