Naringenin Supplementation to a Chow Diet Enhances Energy Expenditure and Fatty Acid Oxidation, and Reduces Adiposity in Lean, Pair‐Fed Ldlr −/− Mice

2019 ◽  
Vol 63 (6) ◽  
pp. 1800833 ◽  
Author(s):  
Amy C. Burke ◽  
Dawn E. Telford ◽  
Jane Y. Edwards ◽  
Brian G. Sutherland ◽  
Cynthia G. Sawyez ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Energy Expenditure ◽  
Fatty Acid Oxidation ◽  
Acid Oxidation ◽  
Chow Diet

Metabolic response to an acute jump in cardiac workload: effects on malonyl-CoA, mechanical efficiency, and fatty acid oxidation

2008 ◽  
Vol 294 (2) ◽  
pp. H954-H960 ◽  
Author(s):  
Lufang Zhou ◽  
Hazel Huang ◽  
Celvie L. Yuan ◽  
Wendy Keung ◽  
Gary D. Lopaschuk ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Energy Expenditure ◽  
Fatty Acid Oxidation ◽  
Mechanical Efficiency ◽  
Acid Oxidation ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa ◽  
Malonyl Coa ◽  
High Workload ◽  
Carnitine Palmitoyltransferase I

Inhibition of myocardial fatty acid oxidation can improve left ventricular (LV) mechanical efficiency by increasing LV power for a given rate of myocardial energy expenditure. This phenomenon has not been assessed at high workloads in nonischemic myocardium; therefore, we subjected in vivo pig hearts to a high workload for 5 min and assessed whether blocking mitochondrial fatty acid oxidation with the carnitine palmitoyltransferase-I inhibitor oxfenicine would improve LV mechanical efficiency. In addition, the cardiac content of malonyl-CoA (an endogenous inhibitor of carnitine palmitoyltransferase-I) and activity of acetyl-CoA carboxylase (which synthesizes malonyl-CoA) were assessed. Increased workload was induced by aortic constriction and dobutamine infusion, and LV efficiency was calculated from the LV pressure-volume loop and LV energy expenditure. In untreated pigs, the increase in LV power resulted in a 2.5-fold increase in fatty acid oxidation and cardiac malonyl-CoA content but did not affect the activation state of acetyl-CoA carboxylase. The activation state of the acetyl-CoA carboxylase inhibitory kinase AMP-activated protein kinase decreased by 40% with increased cardiac workload. Pretreatment with oxfenicine inhibited fatty acid oxidation by 75% and had no effect on cardiac energy expenditure but significantly increased LV power and LV efficiency (37 ± 5% vs. 26 ± 5%, P < 0.05) at high workload. In conclusion, 1) myocardial fatty acid oxidation increases with a short-term increase in cardiac workload, despite an increase in malonyl-CoA concentration, and 2) inhibition of fatty acid oxidation improves LV mechanical efficiency by increasing LV power without affecting cardiac energy expenditure.

scholarly journals Increased Energy Expenditure and Insulin Sensitivity in the High Bone Mass ΔFosB Transgenic Mice

Endocrinology ◽  
2008 ◽  
Vol 150 (1) ◽  
pp. 135-143 ◽  
Author(s):  
Glenn C. Rowe ◽  
Cheol Soo Choi ◽  
Lynn Neff ◽  
William C. Horne ◽  
Gerald I. Shulman ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Insulin Sensitivity ◽  
Energy Expenditure ◽  
Transgenic Mice ◽  
Bone Mass ◽  
Fatty Acid Oxidation ◽  
Acid Oxidation ◽  
High Bone Mass ◽  
Obesity And Diabetes ◽  
Adipose Mass

Obesity and osteoporosis are major health issues affecting millions of individuals. Transgenic mice overexpressing ΔFosB, an activator protein-1 transcription factor, under the control of the enolase 2 (ENO2) promoter exhibit both an increase in bone density and a decrease in adipose mass. Here we demonstrate that ΔFosB overexpression increases fatty-acid oxidation and energy expenditure, leading to a decrease in adipocyte size and adipose mass. In addition, the ENO2-ΔFosB mice exhibit increased insulin sensitivity and glucose tolerance. Targeted overexpression of ΔFosB in adipocytes using the adipocyte protein 2 promoter failed to induce changes in fat or in bone, showing that the effect on metabolic activity is not due to cell-autonomous effects of ΔFosB within adipocytes. Detailed analysis of the ENO2-ΔFosB mice demonstrated that energy expenditure was increased in muscle, independent of locomotor activity. These findings provide evidence that signaling downstream of ΔFosB is a potential target for not only osteoporosis but also obesity and diabetes. Overexpression of ΔFosB under the control of the enolase 2 promoter increases bone mass and energy expenditure by increasing fatty-acid oxidation within muscle, reducing adiposity.

Food withdrawal lowers energy expenditure and induces inactivity in long‐chain fatty acid oxidation–deficient mouse models

2014 ◽  
Vol 28 (7) ◽  
pp. 2891-2900 ◽  
Author(s):  
Eugene F. Diekman ◽  
Michel Weeghel ◽  
Ronald J. A. Wanders ◽  
Gepke Visser ◽  
Sander M. Houten
Keyword(s):  
Fatty Acid ◽  
Energy Expenditure ◽  
Fatty Acid Oxidation ◽  
Mouse Models ◽  
Chain Fatty Acid ◽  
Acid Oxidation ◽  
Deficient Mouse ◽  
Long Chain Fatty Acid ◽  
Long Chain

scholarly journals The SGLT2 inhibitor canagliflozin suppresses lipid synthesis and interleukin-1 beta in ApoE deficient mice

2020 ◽  
Vol 477 (12) ◽  
pp. 2347-2361
Author(s):  
Emily A. Day ◽  
Rebecca J. Ford ◽  
Jessie H. Lu ◽  
Rachel Lu ◽  
Lucie Lundenberg ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Blood Glucose ◽  
Energy Expenditure ◽  
Fatty Acid Oxidation ◽  
Liver Lipid ◽  
Sglt2 Inhibitor ◽  
Lipid Synthesis ◽  
Metabolic Energy ◽  
Metabolic Effects ◽  
Acid Oxidation

Sodium-glucose cotransporter 2 inhibitors such as canagliflozin lower blood glucose and reduce cardiovascular events in people with type 2 diabetes through mechanisms that are not fully understood. Canagliflozin has been shown to increase the activity of the AMP-activated protein kinase (AMPK), a metabolic energy sensor important for increasing fatty acid oxidation and energy expenditure and suppressing lipogenesis and inflammation, but whether AMPK activation is important for mediating some of the beneficial metabolic effects of canagliflozin has not been determined. We, therefore, evaluated the effects of canagliflozin in female ApoE−/− and ApoE−/−AMPK β1−/− mice fed a western diet. Canagliflozin increased fatty acid oxidation and energy expenditure and lowered adiposity, blood glucose and the respiratory exchange ratio independently of AMPK β1. Canagliflozin also suppressed liver lipid synthesis and the expression of ATP-citrate lyase, acetyl-CoA carboxylase and sterol response element-binding protein 1c independently of AMPK β1. Canagliflozin lowered circulating IL-1β and studies in bone marrow-derived macrophages indicated that in contrast with the metabolic adaptations, this effect required AMPK β1. Canagliflozin had no effect on the size of atherosclerotic plaques in either ApoE−/− and ApoE−/−AMPK β1−/− mice. Future studies investigating whether reductions in liver lipid synthesis and macrophage IL-1β are important for the cardioprotective effects of canagliflozin warrant further investigation.

Changes in environmental temperature influence leptin responsiveness in low- and high-fat-fed mice

2007 ◽  
Vol 293 (1) ◽  
pp. R106-R115 ◽  
Author(s):  
Ruth B. S. Harris ◽  
Tiffany D. Mitchell ◽  
Emily W. Kelso ◽  
W. P. Flatt
Keyword(s):  
Fatty Acid ◽  
Food Intake ◽  
Energy Expenditure ◽  
Fatty Acid Oxidation ◽  
Body Fat ◽  
Leptin Resistance ◽  
Positive Energy ◽  
Acid Oxidation ◽  
High Fat ◽  
Hot Environment

Loss of body fat in leptin-treated animals has been attributed to reduced energy intake, increased thermogenesis, and preferential fatty acid oxidation. Leptin does not decrease food intake or body fat in leptin-resistant high-fat (HF)-fed mice, possibly due to a failure of leptin to activate hypothalamic receptors. We measured energy expenditure of male C57BL/6 mice adapted to low-fat (LF) or HF diet and infused them for 13 days with PBS or 10 μg leptin/day from an intraperitoneal miniosmotic pump to test whether leptin resistance prevented leptin-induced increases in energy expenditure and fatty acid oxidation. There was no effect of low-dose leptin infusions on either of these measures in LF-fed or HF-fed mice, even though LF-fed mice lost body fat. Experiment 2 tested leptin responsiveness in LF-fed and HF-fed mice housed at different temperatures (18°C, 23°C, 27°C), assuming that the cold would increase and the hot environment would inhibit food intake and thermogenesis, which could potentially interfere with leptin action. LF-fed mice housed at 23°C were the only mice that lost body fat during leptin infusion, suggesting that an ability to modify energy expenditure is essential to the maintenance of leptin responsiveness. HF-fed mice in cold or warm environments did not respond to leptin. HF-fed mice in the hot environment were fatter than other HF-fed mice, and, surprisingly, leptin caused a further increase in body fat, demonstrating that the mice were not totally leptin resistant and that partial leptin resistance in a hot environment favors positive energy balance and fat deposition.

scholarly journals Acute or Chronic Upregulation of Mitochondrial Fatty Acid Oxidation Has No Net Effect on Whole-Body Energy Expenditure or Adiposity

2010 ◽  
Vol 11 (1) ◽  
pp. 70-76 ◽  
Author(s):  
Kyle L. Hoehn ◽  
Nigel Turner ◽  
Michael M. Swarbrick ◽  
Donna Wilks ◽  
Elaine Preston ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Energy Expenditure ◽  
Fatty Acid Oxidation ◽  
Whole Body ◽  
Acid Oxidation ◽  
Mitochondrial Fatty Acid Oxidation ◽  
Mitochondrial Fatty Acid ◽  
Body Energy

scholarly journals A common East Asian-specific ALDH2 mutation causes obesity and insulin resistance: therapeutic effect of reducing toxic aldehydes by ALDH2 activation

2020 ◽  
Author(s):  
Yi-Cheng Chang ◽  
Hsiao-Lin Lee ◽  
Wenjin Yang ◽  
Meng-Lun Hsieh ◽  
Cai-Cin Liu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Electron Transport ◽  
Energy Expenditure ◽  
Fatty Liver ◽  
Fatty Acid Oxidation ◽  
Water Soluble ◽  
Acid Oxidation ◽  
Diet Induced Obesity ◽  
Brown Adipose

Abstract Obesity and type 2 diabetes have reached pandemic proportion. In particular, the population with diabetes is expected to rise rapidly in East and South Asia. ALDH2 (acetaldehyde dehydrogenase 2, mitochondrial) is the key metabolizing enzyme of acetaldehyde and other toxic aldehydes, such as 4-hydroxynonenal (4-HNE). A missense mutation, Glu504Lys of ALDH2 (denoted as the ALDH2*2 allele) is prevalent in 560 million East Asians, resulting in reduced ALDH2 enzymatic activity. We found that Aldh2*2/*2 homozygous knock-in (KI) mice mimicking human Glu504Lys mutation were prone to develop diet-induced obesity, glucose intolerance, insulin resistance, and fatty liver on a high-fat high-sucrose diet compared with controls. The Aldh2 KI mice demonstrated reduced energy expenditure and thermogenesis. Proteomic analyses of the brown adipose tissue (BAT) of the Aldh2 KI mice identified increased 4-HNE-adducted proteins involved in fatty acid oxidation and electron transport chain. Fatty acid oxidation rate and mitochondrial electron transport activity were reduced in the BAT of the Aldh2 KI mice, which explained the decrease in thermogenesis and energy expenditure. AD-9308 is a water-soluble prodrug of a potent and highly selective ALDH2 activator AD-5591. In vitro, AD-5591 enhanced both WT and mutant ALDH2 enzymatic activities. AD-9308 allosterically activates ALDH2 mainly by partially blocking the substrate exit tunnel, thereby accelerating the substrate-enzyme collision. In vivo, AD-9308 treatment reduced serum 4-HNE levels, ameliorated diet-induced obesity and fatty liver, and improved glucose homeostasis in both Aldh2 WT and KI mice dose-dependently. Our data highlight the therapeutic potential of reducing toxic aldehyde levels by activating ALDH2 for treating metabolic diseases.

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