High Fat low Carb Diets
i have done fat VLCD and LCD (hypercaloric and eucaloric) and they works magically,non fat does not work equally,are inferior.
Mediated by PFKFB3,PDK4,GSY1.
J Clin Endocrinol Metab. 2007 Jan;92(1):284-92.
High-fat/low-carbohydrate diet reduces insulin-stimulated carbohydrate oxidation but stimulates nonoxidative glucose disposal in humans: an important role for skeletal muscle pyruvate dehydrogenase kinase 4.
Chokkalingam K, Jewell K, Norton L, Littlewood J, van Loon LJ, Mansell P, Macdonald IA, Tsintzas K.
Center for Integrated Systems Biology and Medicine, School of Biomedical Sciences, University of Nottingham, Nottingham NG7 2UH, United Kingdom.
Aim: The aim of this report was to study the effect of high-fat (HF)/low-carbohydrate (CHO) diet on regulation of substrate metabolism in humans. Methods: Ten healthy men consumed either a HF (75% energy as fat) or control (35%) diet for 6 d in random order. On d 7, blood glucose disappearance rate (R(d)) was determined before and during a hyperinsulinemic euglyKalpaic clamp. Substrate oxidation was determined by indirect calorimetry. Muscle biopsies were obtained prediet, postdiet, and postclamps. Results: R(d) was similar under basal conditions but slightly elevated ( approximately 10%, P < 0.05) during the last 30 min of the clamp after the HF diet. HF diet reduced CHO oxidation under basal (by approximately 40%, P < 0.05) and clamp conditions (by approximately 20%, P < 0.05), increased insulin-mediated whole-body nonoxidative glucose disposal (by 30%, P < 0.05) and muscle glycogen storage (by approximately 25%, P < 0.05). Muscle pyruvate dehydrogenase complex activity was blunted under basal and clamp conditions after HF compared with control (P < 0.05) and was accompanied by an approximately 2-fold increase (P < 0.05) in pyruvate dehydrogenase kinase 4 (PDK4) mRNA and protein expression. Conclusion: Short-term HF/low-CHO dietary intake did not induce whole-body insulin resistance, but caused a shift in im glucose metabolism from oxidation to glycogen storage. Insulin-stimulated CHO oxidation and muscle pyruvate dehydrogenase complex activity were blunted after the HF diet. Up-regulation of muscle PDK4 expression was an early molecular adaptation to these changes, and we showed for the first time in healthy humans, unlike insulin-resistant individuals, that insulin can suppress PDK4 but not PDK2 gene expression in skeletal muscle.
Metabolism. 2006 Nov;55(11):1457-63.
High-fat/low-carbohydrate diets regulate glucose metabolism via a long-term transcriptional loop.
Sparks LM, Xie H, Koza RA, Mynatt R, Bray GA, Smith SR.
Department of Biological Sciences, Louisiana State University and Agricultural and Mechanical College, Baton Rouge, LA, USA.
Insulin sensitivity is characterized by insulin-stimulated glucose metabolism in skeletal muscle. We hypothesized that carbohydrate metabolism and storage might be under transcriptional control. To test this hypothesis, we fed insulin-sensitive males (glucose disposal rate, 14.7 +/- 4.1 mg/kg fat-free mass [FFM] per minute) an isoenergetic high-fat/low-carbohydrate diet (HF/LCD) for 3 days with muscle biopsies before and after intervention. Oligonucleotide microarrays revealed a total of 369 genes of 18861 genes on the arrays were differentially regulated in response to diet (Bonferonni adjusted P < .01). A similar experiment was conducted in mice with a 3-week intervention using a control group and an HF/LCD group to offset the lack of a control group within the human cohort. As part of an analysis of results previously published from this data set, 7 genes in the carbohydrate metabolism pathway changed in response to the HF/LCD, and 3 genes were confirmed by quantitative reverse transcriptase-polymerase chain reaction: fructose-2,6-biphosphatase 3 (PFKFB3), pyruvate dehydrogenase kinase, isoenzyme 4 (PDK4), and glycogen synthase 1 (muscle). In a separate experiment, we fed C57Bl/6J mice an HF/LCD for 3 weeks and found that the same glucose metabolism genes were changed by approximately 70% on average. Fructose-2,6-biphosphatase 3 and pyruvate dehydrogenase kinase, isoenzyme 4 increased and glycogen synthase 1 (muscle) decreased. Combined, these results suggest a mechanism whereby HF/LCD regulates the genes necessary for glucose utilization and storage vis-a-vis transcriptional control.
Yakugaku Zasshi. 2007 Jan;127(1):153-62.
Transcriptional Regulation of Metabolic Switching PDK4 Gene under Various Physiological Conditions.
Araki M, Nozaki Y, Motojima K.
Department of Biochemistry, Graduate School of Pharmaceutical Sciences, Meiji Pharmaceutical University.
Pyruvate dehydrogenase kinase 4 (PDK4) phosphorylates and inactivates the pyruvate dehydrogenase complex to respond to physiologic conditions. This response switches the energy source from glucose to fatty acids to maintain blood glucose levels.
Obes Res. 2003 Dec;11(12):1471-9.
Dietary regulation of fat oxidative gene expression in different skeletal muscle fiber types.
McAinch AJ, Lee JS, Bruce CR, Tunstall RJ, Hawley JA, Cameron-Smith D.
School of Health Sciences, Deakin University, Burwood, Victoria, Australia.
OBJECTIVE: To determine the effect of a high-fat diet on the expression of genes important for fat oxidation, the protein abundance of the transcription factors peroxisome proliferator-activated receptor (PPAR) isoforms alpha and gamma, and selected enzyme activities in type I and II skeletal muscle. RESEARCH METHODS AND PROCEDURES: Sprague-Dawley rats consumed either a high-fat (HF: 78% energy, n = 8) or high-carbohydrate (64% energy, n = 8) diet for 8 weeks while remaining sedentary. RESULTS: The expression of genes important for fat oxidation tended to increase in both type I (soleus) and type II (extensor digitorum longus) fiber types after an HF dietary intervention. However, the expression of muscle type carnitine palmitoyltransferase I was not increased in extensor digitorum longus. Analysis of the gene expression of both peroxisome proliferator-activated receptor-gamma coactivator and fork-head transcription factor O1 demonstrated no alteration in response to the HF diet. Similarly, PPARalpha and PPARgamma protein levels were also not altered by the HF diet. DISCUSSION: An HF diet increased the expression of an array of genes involved in lipid metabolism, with only subtle differences evident in the response within differing skeletal muscle fiber types.
Br J Nutr. 2002 Jun;87(6):555-9.
The effect of carbohydrate and fat variation in euenergetic diets on postabsorptive free fatty acid release.
Bisschop PH, Ackermans MT, Endert E, Ruiter AF, Meijer AJ, Kuipers F, Sauerwein HP, Romijn JA.
Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, The Netherlands.
Diet composition and energy content modulate free fatty acid (FFA) release. The aim of this study was to evaluate the dose-response effects of euenergetic variations in dietary carbohydrate and fat content on postabsorptive FFA release. The rate of appearance (Ra) of palmitate was measured by infusion of [2,2-2H2]palmitate after an overnight fast in six healthy men on three separate occasions, i.e. after 7 d on euenergetic control, high-carbohydrate and high-fat diets. The protein content and composition was identical for each diet. Postabsorptive plasma fatty acid concentrations were not different between the high-carbohydrate and control diets (0.36 (se 0.07) v. 0.43 (se 0.04) mmol/l), but were increased after the high-fat diet (0.75 (se 0.09) mmol/l, (P<0.01 compared with the other diets). Ra palmitate was not different between the high-carbohydrate and control diets (1.36 (se 0.20) v. 1.47 (se 0.15) micromol/kg per min). However, Ra palmitate was increased to 2.36 (se 0.26) micromol/kg per min after the high-fat diet (P<0.01 compared with the other diets). The fatty acid flux and whole-body fat oxidation were not affected by the high-carbohydrate diet compared with the control diet, but were increased by 67 and 47 % respectively, on the high-fat diet (P<0.01 compared with the other diets). A euenergetic high-fat diet results in increased postabsorptive FFA release and fat oxidation, whereas a euenergetic high-carbohydrate diet does not affect these variables of fat metabolism.
Am J Physiol Endocrinol Metab. 2001 Dec;281(6):E1151-8.
Human skeletal muscle PDH kinase activity and isoform expression during a 3-day high-fat/low-carbohydrate diet.
Peters SJ, Harris RA, Wu P, Pehleman TL, Heigenhauser GJ, Spriet LL.
Department of Human Biology and Nutritional Sciences, University of Guelph, Guelph, Ontario N1G 2W1, Canada.
The increase in skeletal muscle pyruvate dehydrogenase kinase (PDK) activity was measured in skeletal muscle of six healthy males after a eucaloric high-fat/low-carbohydrate (HF/LC; 5% carbohydrate, 73% fat, and 22% protein of total energy intake) diet compared with a standardized prediet (50% carbohdyrate, 30% fat, and 21% protein). Biopsies were obtained from the vastus lateralis muscle after 3 days on the prediet (day 0) and after 1, 2, and 3 days of the HF/LC diet. Intact mitchondria were extracted from fresh muscle and analyzed for PDK activity and Western blotting of PDK2 and PDK4 protein. A second biopsy was taken at each time point and frozen for Northern blot analysis of PDK2 and PDK4 mRNAs. PDK activity increased in a linear fashion over the 3-day HF/LC diet and was significantly higher than control by 1 day. PDK activity was 0.09 +/- 0.03, 0.18 +/- 0.05, 0.30 +/- 0.07, and 0.37 +/- 0.09 min(-1) at 0, 1, 2, and 3 days, respectively. PDK4 protein and mRNA increased maximally by day 1, and PDK2 protein and mRNA were unaffected by the HF/LC diet. Resting respiratory exchange ratios decreased after 1 day of the HF/LC diet (from 0.79 +/- 0.02 to 0.72 +/- 0.02) and remained depressed throughout the 3-day dietary intervention (0.68 +/- 0.01). The immediate shift to fat utilization was accompanied by increased blood glycerol, beta-hydroxybutyrate, and plasma free fatty acid concentrations. These results suggest that the continuing increase in PDK activity over the 3-day HF/LC diet is not due to increasing PDK protein beyond 1 day. This could be due to the contribution of another isoform to the total PDK activity or to a continual increase in PDK4 or PDK2 specific activity.