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

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.

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AMPK and metabolic adaptation by the heart to pressure overload

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00424.2006 ◽

2007 ◽

Vol 292 (1) ◽

pp. H140-H148 ◽

Cited By ~ 42

Author(s):

Michael F. Allard ◽

Hannah L. Parsons ◽

Ramesh Saeedi ◽

Richard B. Wambolt ◽

Roger Brownsey

Keyword(s):

Fatty Acid ◽

Fatty Acid Oxidation ◽

Pressure Overload ◽

Chain Fatty Acid ◽

Metabolic Adaptation ◽

Acid Oxidation ◽

Energy Status ◽

Long Chain Fatty Acid ◽

Ampk Activity ◽

Long Chain

Accelerated glycolysis in hypertrophied hearts may be a compensatory response to reduced energy production from long-chain fatty acid oxidation with 5′-AMP-activated protein kinase (AMPK) functioning as a cellular signal. Therefore, we tested the hypothesis that enhanced fatty acid oxidation improves energy status and normalizes AMPK activity and glycolysis in hypertrophied hearts. Glycolysis, fatty acid oxidation, AMPK activity, and energy status were measured in isolated working hypertrophied and control hearts from aortic-constricted and sham-operated male Sprague-Dawley rats. Hearts from halothane (3–4%)-anesthetized rats were perfused with KH solution containing either palmitate, a long-chain fatty acid, or palmitate plus octanoate, a medium-chain fatty acid whose oxidation is not impaired in hypertrophied hearts. Compared with control, fatty acid oxidation was lower in hypertrophied hearts perfused with palmitate, whereas it increased to similar values in both groups with octanoate plus palmitate. Glycolysis was accelerated in palmitate-perfused hypertrophied hearts and was normalized in hypertrophied hearts by the addition of octanoate. AMPK activity was increased three- to sixfold with palmitate alone and was reduced to control values by octanoate plus palmitate. Myocardial energy status improved with the addition of octanoate but did not differ between groups. Our findings, particularly the correspondence between glycolysis and AMPK activity, provide support for the view that activation of AMPK is responsible, in part, for the acceleration of glycolysis in cardiac hypertrophy. Additionally, they indicate myocardial AMPK is activated by energy state-independent mechanisms in response to pressure overload, demonstrating AMPK is more than a sensor of the heart's energy status.

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Metabolic development in the liver and the implications of the n-3 fatty acid supply

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00189.2011 ◽

2012 ◽

Vol 302 (2) ◽

pp. G250-G259 ◽

Cited By ~ 18

Author(s):

Elizabeth M. Novak ◽

Bernd O. Keller ◽

Sheila M. Innis

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Fatty Acid Oxidation ◽

Maternal Diet ◽

Neonatal Rat ◽

Metabolic Adaptation ◽

Acid Oxidation ◽

Flight Mass Spectrometry ◽

2D Gel ◽

Hepatic Fatty Acid Oxidation

The n-3 fatty acids contribute to regulation of hepatic fatty acid oxidation and synthesis in adults and accumulate in fetal and infant liver in variable amounts depending on the maternal diet fat composition. Using 2D gel proteomics and matrix-assisted laser desorption/ionization time of flight mass spectrometry, we recently identified altered abundance of proteins associated with glucose and amino acid metabolism in neonatal rat liver with increased n-3 fatty acids. Here, we extend studies on n-3 fatty acids in hepatic metabolic development to targeted gene and metabolite analyses and map the results into metabolic pathways to consider the role of n-3 fatty acids in glucose, fatty acid, and amino metabolism. Feeding rats 1.5% compared with <0.1% energy 18:3n-3 during gestation led to higher 20:5n-3 and 22:6n-3 in 3-day-old offspring liver, higher serine hydroxymethyltransferase, carnitine palmitoyl transferase, and acyl CoA oxidase and lower pyruvate kinase and stearoyl CoA desaturase gene expression, with higher cholesterol, NADPH and glutathione, and lower glycine ( P < 0.05). Integration of the results suggests that the n-3 fatty acids may be important in facilitating hepatic metabolic adaptation from in utero nutrition to the postnatal high-fat milk diet, by increasing fatty acid oxidation and directing glucose and amino acids to anabolic pathways.

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NT-PGC-1α deficiency attenuates high-fat diet-induced obesity by modulating food intake, fecal fat excretion and intestinal fat absorption

Scientific Reports ◽

10.1038/s41598-020-79823-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jihyun Kim ◽

Jiyoung Moon ◽

Chul-Hong Park ◽

Jisu Lee ◽

Helia Cheng ◽

...

Keyword(s):

Fatty Acid ◽

Fatty Acid Oxidation ◽

Metabolic Adaptation ◽

Acid Oxidation ◽

High Fat ◽

Male And Female ◽

Diet Induced Obesity ◽

Fecal Fat ◽

Selective Ablation ◽

Fat Excretion

AbstractTranscriptional coactivator PGC-1α and its splice variant NT-PGC-1α regulate metabolic adaptation by modulating many gene programs. Selective ablation of PGC-1α attenuates diet-induced obesity through enhancing fatty acid oxidation and thermogenesis by upregulation of NT-PGC-1α in brown adipose tissue (BAT). Recently, we have shown that selective ablation of NT-PGC-1α reduces fatty acid oxidation in BAT. Thus, the objective of this study was to test our hypothesis that NT-PGC-1α−/− mice would be more prone to diet-induced obesity. Male and female NT-PGC-1α+/+ (WT) and NT-PGC-1α−/− mice were fed a regular chow or 60% high-fat (HF) diet for 16 weeks. Contrary to our expectations, both male and female NT-PGC-1α−/− mice fed HFD were protected from diet-induced obesity, with more pronounced effects in females. This lean phenotype was primarily driven by reduced dietary fat intake. Intriguingly, HFD-fed female, but not male, NT-PGC-1α−/− mice further exhibited decreased feed efficiency, which was closely associated with increased fecal fat excretion and decreased uptake of fatty acids by the intestinal enterocytes and adipocytes with a concomitant decrease in fatty acid transporter gene expression. Collectively, our results highlight the role for NT-PGC-1α in regulating whole body lipid homeostasis under HFD conditions.

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Role of ketone signaling in the hepatic response to fasting

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00415.2017 ◽

2019 ◽

Vol 316 (5) ◽

pp. G623-G631 ◽

Cited By ~ 2

Author(s):

Caroline E. Geisler ◽

Susma Ghimire ◽

Randy L. Bogan ◽

Benjamin J. Renquist

Keyword(s):

Fatty Acid ◽

Mrna Expression ◽

Fatty Acid Oxidation ◽

Uncoupling Protein ◽

Whole Body ◽

Metabolic Adaptation ◽

Acid Oxidation ◽

Transcriptional Level ◽

Nonalcoholic Fatty Liver ◽

Fasting Response

Ketosis is a metabolic adaptation to fasting, nonalcoholic fatty liver disease (NAFLD), and prolonged exercise. β-OH butyrate acts as a transcriptional regulator and at G protein-coupled receptors to modulate cellular signaling pathways in a hormone-like manner. While physiological ketosis is often adaptive, chronic hyperketonemia may contribute to the metabolic dysfunction of NAFLD. To understand how β-OH butyrate signaling affects hepatic metabolism, we compared the hepatic fasting response in control and 3-hydroxy-3-methylglutaryl-CoA synthase II (HMGCS2) knockdown mice that are unable to elevate β-OH butyrate production. To establish that rescue of ketone metabolic/endocrine signaling would restore the normal hepatic fasting response, we gave intraperitoneal injections of β-OH butyrate (5.7 mmol/kg) to HMGCS2 knockdown and control mice every 2 h for the final 9 h of a 16-h fast. In hypoketonemic, HMGCS2 knockdown mice, fasting more robustly increased mRNA expression of uncoupling protein 2 (UCP2), a protein critical for supporting fatty acid oxidation and ketogenesis. In turn, exogenous β-OH butyrate administration to HMGCS2 knockdown mice decreased fasting UCP2 mRNA expression to that observed in control mice. Also supporting feedback at the transcriptional level, β-OH butyrate lowered the fasting-induced expression of HMGCS2 mRNA in control mice. β-OH butyrate also regulates the glycemic response to fasting. The fast-induced fall in serum glucose was absent in HMGCS2 knockdown mice but was restored by β-OH butyrate administration. These data propose that endogenous β-OH butyrate signaling transcriptionally regulates hepatic fatty acid oxidation and ketogenesis, while modulating glucose tolerance. NEW & NOTEWORTHY Ketogenesis regulates whole body glucose metabolism and β-OH butyrate produced by the liver feeds back to inhibit hepatic β-oxidation and ketogenesis during fasting.

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