Effect of short-term fasting on lipolytic responsiveness in normal and obese human subjects

Wolfe, Robert R.; Peters, Edward J.; Klein, Samuel; Holland, O. B.; Rosenblatt, Judah; Gary, Howard E.

doi:10.1152/ajpendo.1987.252.2.e189

Cited by 112 publications

(115 citation statements)

References 5 publications

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“…Interestingly, the decrease in cold-stimulated glucose uptake after fasting is specific for BAT, since this was not observed in other tissues. In subcutaneous WAT, [ 18 F]FDG uptake was increased, which may be explained by an increased triacylglycerol/fatty acid cycling, whereby α-glycerol phosphate, which provides the backbone for esterification of NEFAs, is derived from plasma glucose uptake, as demonstrated previously [35]. The energy required for this process might actually contribute to the increase in energy expenditure that we measured upon fasting [36].…”

Section: Discussionsupporting

confidence: 66%

Glucose uptake in human brown adipose tissue is impaired upon fasting-induced insulin resistance

et al. 2014

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Aims/hypothesis Human brown adipose tissue (BAT) has recently emerged as a potential target in the treatment of type 2 diabetes, owing to its capacity to actively clear glucose from the circulation-at least upon cold exposure. The effects of insulin resistance on the capacity of human BAT to take up glucose are unknown. Prolonged fasting is known to induce insulin resistance in peripheral tissues in order to spare glucose for the brain. Methods We studied the effect of fasting-induced insulin resistance on the capacity of BAT to take up glucose during cold exposure as well as on cold-stimulated thermogenesis. BAT glucose uptake was assessed by means of cold-stimulated dynamic 2-deoxy-2-[ 18 F]fluoro-D-glucose positron emission tomography/computed tomography ([ 18 F]FDG-PET/CT) imaging.Results We show that a 54 h fasting period markedly decreases both cold-induced BAT glucose uptake and nonshivering thermogenesis (NST) during cold stimulation. In vivo molecular imaging and modelling revealed that the reduction of glucose uptake in BAT was due to impaired cellular glucose uptake and not due to decreased supply. Interestingly, decreased BAT glucose uptake upon fasting was related to a decrease in core temperature during cold exposure, pointing towards a role for BAT in maintaining normothermia in humans. Conclusions/interpretation Cold-stimulated glucose uptake in BAT is strongly reduced upon prolonged fasting. When cold-stimulated glucose uptake in BAT is also reduced under other insulin-resistant states, such as diabetes, cold-induced activation of BAT may not be a valid way to improve glucose clearance by BAT under such conditions. Trial registration: www.trialregister.nl NTR3523 Funding: This work was supported by the EU FP7 project DIABAT (HEALTH-F2-2011-278373

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Section: Discussionsupporting

confidence: 66%

Glucose uptake in human brown adipose tissue is impaired upon fasting-induced insulin resistance

et al. 2014

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“…This is in accordance with our previous findings of the readily accessible pool size of VLDL-TAG [22]. VLDL-TAG concentrations and SA were spline fitted to minimise analytical variation that may occur when raw data are used in non-steady-state equations (Sigmaplot 11.0, Systat Software, Chicago, IL, USA) [23]. VLDL-TAG secretion and clearance were calculated according to the following equations [17,18]:…”

Section: Methodssupporting

confidence: 67%

Postprandial VLDL-triacylglycerol secretion is not suppressed in obese type 2 diabetic men

et al. 2012

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Aims/hypothesis Type 2 diabetes is characterised by insulin resistance and increased post-absorptive secretion of VLDLtriacylglycerol (VLDL-TAG). Whether postprandial suppression of endogenous VLDL-TAG secretion is abnormala finding that would link hyperlipidaemia and type 2 diabetes-remains unclear. Methods Eight type 2 diabetic men and eight healthy men were studied before and after a fat-free test meal (40% of resting energy expenditure). VLDL-TAG kinetics were assessed using a primed-constant infusion of ex vivo labelled [1-14 C]triolein VLDL-TAG using non-steadystate calculations. Results Type 2 diabetic men had a higher basal VLDL-TAG secretion rate and concentration than healthy men (mean±SD secretion rate 137±61 vs 78±30 μmol/min, respectively [p00.03]; median concentration 1.03 [range 0.58-1.75] vs 0.33 [0.13-1.14]mmol/l, respectively [p<0.01]). Postprandially, the VLDL-TAG secretion rate decreased in healthy men (p<0.01), but remained unchanged in diabetic men (p00.47). The VLDL-TAG concentration increased in diabetic men and decreased in healthy men postprandially (p<0.05). The difference in VLDL-TAG secretion rate between the two groups approached significance (p00.06) and the relative change in VLDL-TAG secretion rate was significantly different (p00.01) between the two groups. Basal VLDL-TAG clearance was significantly lower in diabetic men (diabetic men 133 [49-390]ml/min; healthy controls 215 ml/min [p<0.05]). After meal ingestion, clearance decreased in healthy men (p00.03), but was unchanged in diabetic men (p00.58). Conclusions/interpretation Obese type 2 diabetic men have impaired postprandial suppression of VLDL-TAG secretion compared with lean healthy men, contributing to their postprandial lipaemia and hypertriacylglycerolaemia.

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“…38 For instance, differences in catecholamines, insulin and adenosine concentrations, and adipose tissue blood¯ow between lean and obese have been reported. 32 ± 34,39 ± 41 Wolfe et al 42 and Webber et al 43 also reported a decreased rate of appearance of FFA per kg fat mass during fasting in obese compared to lean males. However, when expressed per kg of lean body mass, FFA turnover is higher in obese or upper-body obese than in lean or lower body obese subjects 43,44 (Figure 1).…”

Section: Introductionmentioning

confidence: 94%

“…Although resting arterial FFA concentration is usually higher in obese than lean subjects, the increase upon stimulation is often reduced, resulting in similar or even lower FFA concentrations in the obese. 34,42,43 Total and forearm skeletal muscle blood¯ow has been shown to be similar in lean and obese subjects at rest, but adrenaline-or isoprenaline-induced increases in blood¯ow were blunted in the obese. 34,43 Weight loss did not normalise the blunted FFA and blood¯ow response.…”

Section: Fatty Acid Delivery and Transportmentioning

confidence: 99%

“…Also the response of the glycerol and FFA rates of appearance per kg fat mass to adrenaline infusion is signi®cantly blunted in the obese. 42,43 Since there was no difference in the adrenaline-stimulated rate of appearance of FFA when expressed per kg lean body mass between lean and obese, 42,43 Wolfe et al 42 suggested that the blunted response in obese subjects may simply re¯ect the decreased demand to meet the energy requirements of the lean body mass. Unfortunately, the effect of weight loss on the rate of appearance of FFA in obesity has not yet been studied.…”

Section: Introductionmentioning

confidence: 99%

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Exercise training and substrate utilisation in obesity

Baak

1999

Int J Obes

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Together with diet and behavioural modi®cation, regular exercise is one of the key components of programs for the treatment of obesity. It appears to be one of the major factors determining the long-term success of weight loss programs. One of the mechanisms that may underlie this and other bene®cial effects of regular exercise is the effect of exercise training on substrate utilisation. Exercise training increases fat oxidation in lean subjects. The capacity to mobilise and oxidise fat has been shown to be impaired in obese and post-obese subjects. Thus, an increase in the capacity for fat oxidation may help to maintain fat and energy balance at a lower fat mass in individuals with a predisposition for obesity. However, in view of the impaired fat oxidation in obese and post-obese individuals the question arises whether exercise training also increases fat oxidation in the obese. Few studies have addressed this question and have investigated the effect of exercise training on substrate utilisation in obesity. Addition of an exercise training program has been shown to prevent the reduction of basal fat oxidation that is associated with dietinduced weight loss in two studies. No effect of additional exercise training on substrate oxidation during exercise was found. In post-obese subjects exercise training caused no change in 24 h substrate oxidation in one study and increased carbohydrate, rather than fat oxidation in another. In obese subjects neither low (40% maximal aerobic ®tness (VO 2 max)) nor high (70% VO 2 max) intensity training was found to affect resting substrate oxidation. During exercise fractional fat oxidation was increased after low, but not after high intensity training. The question, whether exercise training increases fat oxidation in obese and post-obese as in lean subjects therefore cannot be answered conclusively at this point in time and requires further study. The role of exercise intensity and type of exercise needs to be studied as well.

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Effect of short-term fasting on lipolytic responsiveness in normal and obese human subjects

Cited by 112 publications

References 5 publications

Glucose uptake in human brown adipose tissue is impaired upon fasting-induced insulin resistance

Glucose uptake in human brown adipose tissue is impaired upon fasting-induced insulin resistance

Postprandial VLDL-triacylglycerol secretion is not suppressed in obese type 2 diabetic men

Exercise training and substrate utilisation in obesity

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