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      Gluconeogenesis during endurance exercise in cyclists habituated to a long‐term low carbohydrate high‐fat diet

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          Abstract

          Key points

          • Blood glucose is an important fuel for endurance exercise. It can be derived from ingested carbohydrate, stored liver glycogen and newly synthesized glucose (gluconeogenesis).

          • We hypothesized that athletes habitually following a low carbohydrate high fat (LCHF) diet would have higher rates of gluconeogenesis during exercise compared to those who follow a mixed macronutrient diet.

          • We used stable isotope tracers to study glucose production kinetics during a 2 h ride in cyclists habituated to either a LCHF or mixed macronutrient diet.

          • The LCHF cyclists had lower rates of total glucose production and hepatic glycogenolysis but similar rates of gluconeogenesis compared to those on the mixed diet.

          • The LCHF cyclists did not compensate for reduced dietary carbohydrate availability by increasing glucose synthesis during exercise but rather adapted by altering whole body substrate utilization.

          Abstract

          Endogenous glucose production (EGP) occurs via hepatic glycogenolysis (GLY) and gluconeogenesis (GNG) and plays an important role in maintaining euglycaemia. Rates of GLY and GNG increase during exercise in athletes following a mixed macronutrient diet; however, these processes have not been investigated in athletes following a low carbohydrate high fat (LCHF) diet. Therefore, we studied seven well‐trained male cyclists that were habituated to either a LCHF (7% carbohydrate, 72% fat, 21% protein) or a mixed diet (51% carbohydrate, 33% fat, 16% protein) for longer than 8 months. After an overnight fast, participants performed a 2 h laboratory ride at 72% of maximal oxygen consumption. Glucose kinetics were measured at rest and during the final 30 min of exercise by infusion of [6,6‐ 2H 2]‐glucose and the ingestion of 2H 2O tracers. Rates of EGP and GLY both at rest and during exercise were significantly lower in the LCHF group than the mixed diet group (Exercise EGP: LCHF, 6.0 ± 0.9 mg kg −1 min −1, Mixed, 7.8 ± 1.1 mg kg −1 min −1, P < 0.01; Exercise GLY: LCHF, 3.2 ± 0.7 mg kg −1 min −1, Mixed, 5.3 ± 0.9 mg kg −1 min −1, P < 0.01). Conversely, no difference was detected in rates of GNG between groups at rest or during exercise (Exercise: LCHF, 2.8 ± 0.4 mg kg −1 min −1, Mixed, 2.5 ± 0.3 mg kg −1 min −1, P = 0.15). We conclude that athletes on a LCHF diet do not compensate for reduced glucose availability via higher rates of glucose synthesis compared to athletes on a mixed diet. Instead, GNG remains relatively stable, whereas glucose oxidation and GLY are influenced by dietary factors.

          Key points

          • Blood glucose is an important fuel for endurance exercise. It can be derived from ingested carbohydrate, stored liver glycogen and newly synthesized glucose (gluconeogenesis).

          • We hypothesized that athletes habitually following a low carbohydrate high fat (LCHF) diet would have higher rates of gluconeogenesis during exercise compared to those who follow a mixed macronutrient diet.

          • We used stable isotope tracers to study glucose production kinetics during a 2 h ride in cyclists habituated to either a LCHF or mixed macronutrient diet.

          • The LCHF cyclists had lower rates of total glucose production and hepatic glycogenolysis but similar rates of gluconeogenesis compared to those on the mixed diet.

          • The LCHF cyclists did not compensate for reduced dietary carbohydrate availability by increasing glucose synthesis during exercise but rather adapted by altering whole body substrate utilization.

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          Most cited references29

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          Major types of dietary fat and risk of coronary heart disease: a pooled analysis of 11 cohort studies.

          Saturated fatty acid (SFA) intake increases plasma LDL-cholesterol concentrations; therefore, intake should be reduced to prevent coronary heart disease (CHD). Lower habitual intakes of SFAs, however, require substitution of other macronutrients to maintain energy balance. We investigated associations between energy intake from monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids (PUFAs), and carbohydrates and risk of CHD while assessing the potential effect-modifying role of sex and age. Using substitution models, our aim was to clarify whether energy from unsaturated fatty acids or carbohydrates should replace energy from SFAs to prevent CHD. This was a follow-up study in which data from 11 American and European cohort studies were pooled. The outcome measure was incident CHD. During 4-10 y of follow-up, 5249 coronary events and 2155 coronary deaths occurred among 344,696 persons. For a 5% lower energy intake from SFAs and a concomitant higher energy intake from PUFAs, there was a significant inverse association between PUFAs and risk of coronary events (hazard ratio: 0.87; 95% CI: 0.77, 0.97); the hazard ratio for coronary deaths was 0.74 (95% CI: 0.61, 0.89). For a 5% lower energy intake from SFAs and a concomitant higher energy intake from carbohydrates, there was a modest significant direct association between carbohydrates and coronary events (hazard ratio: 1.07; 95% CI: 1.01, 1.14); the hazard ratio for coronary deaths was 0.96 (95% CI: 0.82, 1.13). MUFA intake was not associated with CHD. No effect modification by sex or age was found. The associations suggest that replacing SFAs with PUFAs rather than MUFAs or carbohydrates prevents CHD over a wide range of intakes.
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            Interleukin-6 is a novel factor mediating glucose homeostasis during skeletal muscle contraction.

            The mechanisms that mediate the tightly controlled production and clearance of glucose during muscular work are unclear, and it has been suggested that an unidentified "work factor" exists that influences the contraction-induced increase in endogenous glucose production (EGP). The cytokine interleukin (IL)-6 is released from skeletal muscle during contraction. Here we show that IL-6 contributes to the contraction-induced increase in EGP. Six men performed 2 h of bicycle exercise on three separate occasions, at a relatively high intensity (HI) or at a low intensity with (LO + IL-6) or without (LO) an infusion of recombinant human IL-6 that matched the circulating concentration of IL-6 seen in HI exercise. The stable isotope 6,6 (2)H(2) glucose was infused to calculate EGP (rate of glucose appearance [R(a)]), whole-body glucose disposal (rate of glucose disappearance [R(d)]), and metabolic clearance rate (MCR) of glucose. Glucose R(a), R(d), and MCR were higher (P < 0.05) at HI than at LO. Throughout exercise at LO + IL-6, glucose R(a) and R(d) were higher (P < 0.05) than LO, even though the exercise intensity was identical. In addition, MCR was higher (P < 0.05) at LO + IL-6 than at LO at 90 min. Insulin, glucagon, epinephrine, norepinephrine, cortisol, and growth hormone were identical when comparing LO + IL-6 with LO. These data suggest that IL-6 influences glucose homeostasis during exercise. Our results provide potential new insights into factors that mediate glucose production and disposal and implicates IL-6 in the so-called "work factor."
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              Is Open Access

              Ketosis, ketogenic diet and food intake control: a complex relationship

              Though the hunger-reduction phenomenon reported during ketogenic diets is well-known, the underlying molecular and cellular mechanisms remain uncertain. Ketosis has been demonstrated to exert an anorexigenic effect via cholecystokinin (CCK) release while reducing orexigenic signals e.g., via ghrelin. However, ketone bodies (KB) seem to be able to increase food intake through AMP-activated protein kinase (AMPK) phosphorylation, gamma-aminobutyric acid (GABA) and the release and production of adiponectin. The aim of this review is to provide a summary of our current knowledge of the effects of ketogenic diet (KD) on food control in an effort to unify the apparently contradictory data into a coherent picture.
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                Author and article information

                Journal
                J Physiol
                J. Physiol. (Lond.)
                10.1111/(ISSN)1469-7793
                TJP
                jphysiol
                The Journal of Physiology
                John Wiley and Sons Inc. (Hoboken )
                0022-3751
                1469-7793
                08 June 2016
                01 August 2016
                : 594
                : 15 ( doiID: 10.1113/tjp.2016.594.issue-15 )
                : 4389-4405
                Affiliations
                [ 1 ] Division of Exercise Science and Sports Medicine (ESSM), Department of Human Biology, Faculty of Health Sciences University of Cape Town Newlands South Africa
                [ 2 ] Department of Pediatrics, Children's Nutrition Research Center, US Department of Agriculture/Agricultural Research Service Baylor College of Medicine Houston TX USA
                Author notes
                [*] [* ] Corresponding author J. Smith: Private Bag X3, Rondebosch, Cape Town 7701, South Africa. Email: ja.smith@ 123456uct.ac.za
                Author information
                http://orcid.org/0000-0003-2769-4316
                Article
                PMC4967730 PMC4967730 4967730 TJP7175
                10.1113/JP271934
                4967730
                26918583
                8ae62ab2-77a2-49a0-a561-a99058180799
                © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society
                History
                : 23 November 2015
                : 23 February 2016
                Page count
                Pages: 17
                Categories
                Metabolism and Regulation
                Endurance and Performance
                Exercise Metabolism
                Research Paper
                Integrative
                Custom metadata
                2.0
                tjp7175
                1 August 2016
                Converter:WILEY_ML3GV2_TO_NLMPMC version:4.9.2 mode:remove_FC converted:01.08.2016

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