Effects of Fasting on Fatty Acid Kinetics and on the Cardiovascular, Thermogenic and Metabolic Responses to the Glucose Clamp

Webber, Jonathan; Taylor, Julian; Greathead, H.M.R.; Dawson, J. M.; Buttery, P. J.; Macdonald, I. A.

doi:10.1042/cs0870697

Cited by 35 publications

(32 citation statements)

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“…Starvation has consistently been shown to decrease IS and deteriorate postprandial glucose tolerance. 7,8,17 Similarly, further studies have demonstrated a decline in clamp-derived IS within 24 h (200 kcal per day) and 5 days (À50% energy) of CR, respectively. 10,11 Severe carbohydrate restriction induces postprandial hyperglycemia and IR at skeletal muscle to shift fuel to the brain.…”

Section: Discussionmentioning

confidence: 90%

“…Fasting (1 --3 days) consistently caused a decline in IS assessed by clamp-and intravenous glucose tolerance test. 7,8,17 Studies with less severe CR, however, provided rather inconsistent results. Although some studies have found an impairment of IS within 1 --5 days of CR (p50% energy) in healthy lean subjects, 10,11 clamp-derived IS has been shown to be sustained following 7 days of CR at an energy intake of 60 kJ kg À1 body weight per day.…”

Section: Introductionmentioning

confidence: 99%

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Effects of brief perturbations in energy balance on indices of glucose homeostasis in healthy lean men

et al. 2011

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BACKGROUND:Little is known about the effects of short-term caloric restriction (CR) and overfeeding (OF) on glucose homeostasis in healthy lean individuals. In addition, it remains unclear whether the effects of CR and OF are reversed by a complementary feeding period. METHODS: Ten healthy men participated in two cycles of controlled 7-day periods of CR and refeeding (RF; protocol A), and OF and CR (protocol B) at ±60% energy requirement. At baseline, insulin sensitivity (IS) was assessed by euglycemic clamp (M). Before and during each feeding cycle, fasting and oral glucose tolerance test-derived indices were used to estimate glucose tolerance, IS and glucose-stimulated insulin secretion. RESULTS: Clamp tests revealed normal IS at baseline (M-values 9.4 ± 2.1 mg kg À1 min À1 , coefficient of variation (CV) inter 22%). M-values were significantly correlated with indices of IS. In protocol A, CR-induced weight loss (À3.0±0.4 kg) was associated with an increase in fasting IS. Postprandial IS and glucose-stimulated insulin secretion remained unchanged, but glucose tolerance decreased. RF decreased fasting and postprandial IS at increased glucose-stimulated insulin secretion. In protocol B, OF significantly increased the body weight ( þ 1.6±0.9 kg). Concomitantly, fasting and postprandial IS decreased at increased glucose-stimulated insulin secretion. Subsequent CR reversed these effects. Inter-individual variability in indices of glucose metabolism was high with coefficients of variation ranging from 9 to 59%. CONCLUSION: Significant changes in glucose metabolism are evident within 7-day periods of controlled OF and underfeeding. Although IS was impaired at the end of the CR --RF cycle, IS was normalized after the OF --CR cycle. At different feeding regimens, homeostatic responses of glucose metabolism were highly variable. Keywords: insulin secretion; insulin sensitivity; glucose homeostasis; weight gain; energy balance INTRODUCTION Long-term perturbations in energy balance, either by overfeeding (OF) or underfeeding, are known to modulate insulin sensitivity (IS). Chronic OF and obesity are commonly characterized by insulin resistance, 1 which has been shown to be completely 2 or partially reversed by acute caloric restriction (CR), as well as by moderate weight loss. 3 --5 On the other hand, IS is preserved or even improved with chronic CR in patients with anorexia nervosa and returned to normal values at the end of refeeding (RF). 6 Although considerable research has been devoted to individuals outside the normal range of body weight, there are only few studies examining the effects of short-term controlled perturbations in energy balance on IS in lean subjects without confounding metabolic abnormalities. 7 --17 Moreover, these studies provide discordant findings that may depend on duration and degree of energy imbalance and macronutrient composition of the diets. Fasting (1 --3 days) consistently caused a decline in IS assessed by clamp-and intravenous glucose tolerance test. 7,8,17 Studies with less severe ...

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Section: Discussionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Effects of brief perturbations in energy balance on indices of glucose homeostasis in healthy lean men

et al. 2011

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“…Although we did not compare glucose sensitivity before and after the fast, it is known that fasting inhibits insulin-mediated whole body oxidative glucose disposal (25,47), presumably via operation of the glucose-fatty acid cycle (32). However, when FFAs are available in excess after lipid-heparin infusion, glucose 6-phosphate levels fall below control levels, suggesting inhibition of glucose transport/phosphorylation rather than via elevation of acetyl-CoA/CoA and NADH/ NAD ϩ (34).…”

Section: Discussionmentioning

confidence: 93%

“…Three to four days of fasting results in elevated plasma FFA concentration (15, 47) and impaired glucose uptake (25,47). However, the glucose-"sparing" effect in this condition is understood to be mediated by the increase in circulating ketones, whose metabolism inhibits hexokinase via operation of the glucose-fatty acid cycle (32).…”

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confidence: 99%

Fasting for 72 h increases intramyocellular lipid content in nondiabetic, physically fit men

Stannard

Thompson

Fairbairn

et al. 2002

American Journal of Physiology-Endocrinology and Metabolism

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, undertook a water-only fast for 84 h. Vastus lateralis IMCL content was determined using proton magnetic resonance spectroscopy after 12 and 84 h of fasting. Venous blood was sampled at 12-h intervals throughout the fast. IMCL-(CH2)n/water and IMCL-(CH2)n/total creatine ratios increased from 0.00623 Ϯ 0.00065 to 0.0142 Ϯ 0.0015 (P ϭ 0.002) and 6.82 Ϯ 0.87 to 14.96 Ϯ 1.73 (P ϭ 0.001), respectively. Plasma free fatty acid (FFA), serum triglyceride, and whole blood 3-hydroxybutyrate concentrations increased (P Ͻ 0.001, Ͻ0.05, Ͻ0.03, respectively), whereas plasma glucose and serum insulin concentrations decreased (both P Ͻ 0.001) during fasting. In conclusion, 72-h water-only fasting produces a large increase in plasma FFA concentration, a drop in serum insulin concentration, and accumulation of IMCL in the vastus lateralis muscle of nondiabetic, physically fit men. muscle triglyceride; free fatty acids; insulin TYPE 2 DIABETIC PATIENTS show an increase in resting intramyocellular lipid (IMCL) content (14). Correspondingly, insulin sensitivity alone in nondiabetic humans appears to be well predicted by IMCL content, as determined from muscle biopsy samples (24, 31) or proton magnetic resonance spectroscopy ( 1 H-MRS) (23). It is not clear whether the increase in IMCL is a cause or an effect of insulin resistance, although it has been recently suggested that a very high content of IMCL creates a physical barrier to GLUT4 translocation (21).In normal-weight nondiabetics, fasting plasma free fatty acid (FFA) concentration is correlated inversely with whole body insulin-stimulated glucose uptake (23) and positively with IMCL content (8). Indeed, an acute increase in plasma FFA concentration is associated with reduced insulin sensitivity and increased IMCL content (3, 4), whereas an acute reduction in FFA concentration improves insulin sensitivity (36).Three to four days of fasting results in elevated plasma FFA concentration (15, 47) and impaired glucose uptake (25,47). However, the glucose-"sparing" effect in this condition is understood to be mediated by the increase in circulating ketones, whose metabolism inhibits hexokinase via operation of the glucose-fatty acid cycle (32).The effect of fasting on IMCL content is equivocal in animals (17) and unknown in humans. However, in 60-h-fasted nonobese men, whole body FFA esterification appears in excess of splanchnic FFA uptake, esterification, and release as triglyceride (20), suggesting an unidentified nonhepatic site of triglyceride accumulation, possibly muscle. Furthermore, 3-hydroxybutyrate infusion into the brachial artery arrests the release of glycerol and FFAs from deep forearm veins (49), suggesting cessation of intramuscular lipolysis. Arterial concentrations of 3-hydroxybutyrate substantially increase during fasting (30). Thus it is conceivable that the reduced insulin-mediated glucose uptake during fasting may be mediated, at least in part, by an increase in IMCL content.It was, therefore, the objective of the present study to test the hypothesis that a pr...

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“…The availability of the glucose clamp technique in combination with indirect calorimetry to assess CHO oxidation has allowed this to be studied in more detail. It is now clear that the insulin resistance produced by acute starvation (up to 72 h) is entirely due to a decrease in the ability of insulin to stimulate CHO oxidation (Mansell & Macdonald, 1990;Webber et al, 1994). In healthy subjects who starve for up to 72 h, insulin stimulated glucose disposal is reduced by up to 50%.…”

Section: Dietary Cho and Glucose Tolerancementioning

confidence: 99%

Carbohydrate as a nutrient in adults: range of acceptable intakes

Macdonald

1999

Eur J Clin Nutr

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This review considers the acute and chronic effects of different levels of carbohydrate (CHO) intakes. The type of CHO consumed, especially glucose vs fructose, affects the glycaemic, insulinaemic and thermogenic responses. In addition, other aspects of food (type of starch, method of processing or cooking, presence of other nutrients) affects the glycaemic response (glycaemic index). In general, the greatest bene®t to health is derived from consuming foods with a low glycaemic index and a high non-starch polysaccharide (®bre) content. Healthy, moderately active adults require at least 200 g CHO per day to sustain normal brain metabolism and muscle function. Moreover, the CHO content should represent at least 50% of energy intake. Higher intakes of CHO can have deleterious effects on blood lipids (especially plasma triacylglycerol) in middle-aged and elderly subjects, and are really only appropriate for subjects with a high level of physical activity who need to maintain muscle glycogen content. Meals with a high carbohydrate content can lead to problems of postprandial hypotension in the elderly, and impaired exercise capacity in patients with angina.

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Effects of Fasting on Fatty Acid Kinetics and on the Cardiovascular, Thermogenic and Metabolic Responses to the Glucose Clamp

Cited by 35 publications

References 0 publications

Effects of brief perturbations in energy balance on indices of glucose homeostasis in healthy lean men

Effects of brief perturbations in energy balance on indices of glucose homeostasis in healthy lean men

Fasting for 72 h increases intramyocellular lipid content in nondiabetic, physically fit men

Carbohydrate as a nutrient in adults: range of acceptable intakes

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