The effects of underfeeding on whole‐body carbohydrate partitioning, thermogenesis and uncoupling protein 3 expression in human skeletal muscle

Seevaratnam, N; Bennett, Andrew J.; Webber, Jonathan; Macdonald, I. A.

doi:10.1111/j.1463-1326.2006.00646.x

Cited by 6 publications

(5 citation statements)

References 26 publications

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“…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. 41 As to the mechanisms, increased FFA availability through increased lipolysis (Table 2 and 3), together with endocrine alterations (e.g., elevated growth hormone levels) and stress-response 42 add to impair IS.…”

Section: Discussionmentioning

confidence: 99%

“…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. 9 By contrast, long-term CR has been shown to improve fasting and oral glucose tolerance test (OGTT)-derived indices of IS.…”

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: 99%

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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“…Even when animal models of dietary-induced obesity are considered, there is little or no stratification of obese animals in terms of phenotype or gene expression. A considerable amount of research effort is currently being put into the development of drugs to enhance fat metabolism in obese subjects -the central hypothesis is that obesity is associated with impaired fat metabolism (18,19). However, the findings from our study demonstrate that some obese individuals have a considerably higher fat oxidation capacity than lean individuals.…”

Section: Variability In Human Cells and Subjects: Goldmine Or Gordianmentioning

confidence: 53%

The use of Human Tissues and Cells in Biomedical Research: The Unusual Suspects

Bennett

2010

Altern Lab Anim

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There are compelling reasons to search for alternatives to the use of animals in medical and pharmaceutical research. Aside from the obvious animal welfare issues, both the well-established differences between animal models and humans, and the inherent inter-individual variability in human biological responses, indicate that human-based alternatives are urgently required. However, any such alternative must out-perform the animal-based alternative, otherwise there will be little or no uptake and adoption by end-users. Data obtained from inbred animal models is often highly reproducible, and is therefore attractive to researchers in the fields of biomedical and pharmaceutical research. The inter-individual variability observed during human volunteer and human tissue-based studies is often considered to be problematic, and has been highlighted further with the advent of the ‘omics’ technologies, which generate large biological datasets. However, the variability in both baseline data and response to pharmacological or toxicological challenge observed in human tissues potentially contains a veritable gold mine of information, which may be critical for the advancement of drug discovery.

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“…However, the effects of short-term caloric restriction are different. In one study, 11 subjects were fed for two periods of 6 days with hypo- and eucaloric diet with the same macronutrient composition in random order [34]. At 6 days, fasting FFAs significantly increased with the hypocaloric diet compared with the eucaloric diet [34].…”

Section: Discussionmentioning

confidence: 99%

“…In one study, 11 subjects were fed for two periods of 6 days with hypo- and eucaloric diet with the same macronutrient composition in random order [34]. At 6 days, fasting FFAs significantly increased with the hypocaloric diet compared with the eucaloric diet [34]. Whether the macronutrient composition affects FFAs was investigated in an animal model, and the study found that energy-restricted high-fat versus low-fat diet did not result in different FFA levels [35].…”

Section: Discussionmentioning

confidence: 99%

Free Fatty Acids’ Level and Nutrition in Critically Ill Patients and Association with Outcomes: A Prospective Sub-Study of PermiT Trial

et al. 2019

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Objectives: The objectives of this study were to evaluate the clinical and nutritional correlates of high free fatty acids (FFAs) level in critically ill patients and the association with outcomes, and to study the effect of short-term caloric restriction (permissive underfeeding) on FFAs level during critical illness. Patients/Method: In this pre-planned sub-study of the PermiT (Permissive Underfeeding vs. Target Enteral Feeding in Adult Critically Ill Patients) trial, we included critically ill patients who were expected to stay for ≥14 days in the intensive care unit. We measured FFAs level on day 1, 3, 5, 7, and 14 of enrollment. Of 70 enrolled patients, 23 (32.8%) patients had high FFAs level (baseline FFAs level >0.45 mmol/L in females and >0.6 mmol/L in males). Results: Patients with high FFAs level were significantly older and more likely to be females and diabetics and they had lower ratio of partial pressure of oxygen to the fraction of inspired oxygen, higher creatinine, and higher total cholesterol levels than those with normal FFAs level. During the study period, patients with high FFAs level had higher blood glucose and required more insulin. On multivariable logistic regression analysis, the predictors of high baseline FFAs level were diabetes (adjusted odds ratio (aOR): 5.36; 95% confidence interval (CI): 1.56, 18.43, p = 0.008) and baseline cholesterol level (aOR, 4.29; 95% CI: 11.64, 11.19, p = 0.003). Serial levels of FFAs did not differ with time between permissive underfeeding and standard feeding groups. FFAs level was not associated with 90-day mortality (aOR: 0.49; 95% CI: 0.09, 2.60, p = 0.40). Conclusion: We conclude that high FFAs level in critically ill patients is associated with features of metabolic syndrome and is not affected by short-term permissive underfeeding.

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The effects of underfeeding on whole‐body carbohydrate partitioning, thermogenesis and uncoupling protein 3 expression in human skeletal muscle

Cited by 6 publications

References 26 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

The use of Human Tissues and Cells in Biomedical Research: The Unusual Suspects

Free Fatty Acids’ Level and Nutrition in Critically Ill Patients and Association with Outcomes: A Prospective Sub-Study of PermiT Trial

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