[Show abstract][Hide abstract] ABSTRACT: The intestine is the main site for glucose absorption and it has been suggested that it exhibits insulin resistance. Bariatric surgery has been shown to reverse insulin resistance and type 2 diabetes, but its effects on human intestinal metabolism are unknown. Our aim was to evaluate the effects of insulin on intestinal glucose metabolism before and after bariatric surgery.
Twenty-one morbidly obese individuals undergoing bariatric surgery and ten age-matched healthy individuals were recruited and intestinal and skeletal muscle glucose uptake (GU) was measured using [(18)F]fluoro-2-deoxyglucose and positron emission tomography at fast and during hyperinsulinaemia. MRI was used as anatomical reference. Obese participants were studied again 6 months postoperatively.
In contrast to healthy individuals, insulin had no effect on intestinal GU in obese participants with or without diabetes, suggesting that intestinal insulin resistance is present early in morbid obesity. Postoperatively, jejunal GU increased in line with whole-body and muscle GU. Postoperative GU values in the intestine correlated with whole-body insulin sensitivity, indicating that the intestinal mucosa may reflect the overall glycaemic state and potentially mediate obesity-associated insulin resistance.
This study shows that insulin is a potent stimulator of GU in the healthy intestine and that intestinal insulin resistance is ameliorated after bariatric surgery. In our study, obese individuals had intestinal insulin resistance regardless of their glycaemic status. Persistent changes in intestinal glucose metabolism are likely to influence both local processes in the gut and systemic glucose homeostasis.
[Show abstract][Hide abstract] ABSTRACT: Aims/hypothesis
Obesity causes an imbalance in fat mass distribution between visceral and subcutaneous adipose tissue (AT) depots. We tested the hypothesis that this relates to increased NEFA uptake between these depots in obese compared with healthy participants. Second, we hypothesised that a diet very low in energy (very low calorie diet [VLCD]) decreases fat mass in obese participants and that this is associated with the decline in NEFA uptake.
NEFA uptake in AT depots was measured with [18F]-fluoro-6-thia-heptadecanoic acid (18F-FTHA) and positron emission tomography (PET) in 18 obese participants with the metabolic syndrome before and after a 6 week VLCD. Whole body fat oxidation was measured using indirect calorimetry and [U-13C]palmitate. Sixteen non-obese participants were controls.
Obese participants had >100% higher (p
[Show abstract][Hide abstract] ABSTRACT: The aim of the present study was to analyse the agreement of bioelectrical impedance analysis (BIA) compared with dual-energy X-ray absorptiometry (DXA) and MRI in estimating body fat, skeletal muscle and visceral fat during a 12-month weight loss intervention. A total of nineteen obese adults (twelve females, seven males) aged 20·2-48·6 years, mean BMI 34·6 (se 0·6) kg/m2, participated in the study. Body fat, skeletal muscle and visceral fat index were measured by BIA (Omron BF-500; Omron Medizintechnik) and compared with DXA (body fat and skeletal muscle) at baseline, 5 and 12 months, and with MRI (visceral fat) at baseline and 5 months. The subjects lost 8·9 (se 1·8) kg (9·0 (se 1·7) %) of body weight during the 12-month intervention. BIA, as compared to DXA, accurately assessed loss of fat (7·0 (se 1·5) v. 7·0 (se 1·4) kg, P = 0·94) and muscle (1·0 (se 0·2) v. 1·4 (se 0·3) kg, P = 0·18). While body fat was similar by the two methods, skeletal muscle was underestimated by 1-2 kg using BIA at each time point. Compared to MRI, BIA overestimated visceral fat, especially in males. BIA and DXA showed high correlations for kg fat, both cross-sectionally and longitudinally (r 0·91-0·99). BIA, compared with DXA and MRI, detected kg muscle and visceral fat more accurately cross-sectionally (r 0·77-0·87 and r 0·40-0·78, respectively) than their changes longitudinally (r 0·24-0·61 and r 0·46, respectively). BIA is at its best when assessing the amount or changes in fat mass. It is a useful method for measuring skeletal muscle, but limited in its ability to measure visceral fat.
The British journal of nutrition 08/2012; 109(10):1-7. DOI:10.1017/S0007114512003698 · 3.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To test whether brain fatty acid uptake is enhanced in obese subjects with metabolic syndrome (MS) and whether weight reduction modifies it.
We measured brain fatty acid uptake in a group of 23 patients with MS and 7 age-matched healthy control subjects during fasting conditions using positron emission tomography (PET) with [(11)C]-palmitate and [(18)F]fluoro-6-thia-heptadecanoic acid ([(18)F]-FTHA). Sixteen MS subjects were restudied after 6 weeks of very low calorie diet intervention.
At baseline, brain global fatty acid uptake derived from [(18)F]-FTHA was 50% higher in patients with MS compared with control subjects. The mean percentage increment was 130% in the white matter, 47% in the gray matter, and uniform across brain regions. In the MS group, the nonoxidized fraction measured using [(11)C]-palmitate was 86% higher. Brain fatty acid uptake measured with [(18)F]-FTHA-PET was associated with age, fasting serum insulin, and homeostasis model assessment (HOMA) index. Both total and nonoxidized fractions of fatty acid uptake were associated with BMI. Rapid weight reduction decreased brain fatty acid uptake by 17%.
To our knowledge, this is the first study on humans to observe enhanced brain fatty acid uptake in patients with MS. Both fatty acid uptake and accumulation appear to be increased in MS patients and reversed by weight reduction.
[Show abstract][Hide abstract] ABSTRACT: Obesity is associated with increased fatty acid uptake in the myocardium, and this may have deleterious effects on cardiac function. The aim of this study was to evaluate how weight loss influences myocardial metabolism and cardiac work in obese adults. Thirty-four obese (mean body mass index 33.7 +/- 0.7 kg/m(2)) but otherwise healthy subjects consumed a very low calorie diet for 6 weeks. Cardiac substrate metabolism and work were measured before and after the diet. Myocardial fatty acid uptake was measured in 18 subjects using fluorine-18-fluoro-6-thia-heptadecanoic acid and positron emission tomography, and myocardial glucose uptake was measured in 16 subjects using fluorine-18-2-fluoro-2-deoxyglucose. Myocardial structure and cardiac function were measured using magnetic resonance imaging. Consumption of the very low calorie diet decreased weight (-11.2 +/- 0.6 kg, p <0.0001). Myocardial fatty acid uptake decreased from 4.2 +/- 0.4 to 2.9 +/- 0.2 micromol/100 g/min (p <0.0001). Myocardial mass decreased by 7% (p <0.005), and cardiac work decreased by 26% (p <0.0001). Whole-body insulin sensitivity increased by 33% (p <0.01), but insulin-stimulated myocardial glucose uptake remained unchanged (p = 0.90). Myocardial triglyceride content decreased by 31% (n = 8, p = 0.076). In conclusion, weight reduction decreases myocardial fatty acid uptake in parallel with myocardial mass and cardiac work. These results show that the increased fatty acid uptake found in the hearts of obese patients can be reversed by weight loss.
The American journal of cardiology 06/2009; 103(12):1721-6. DOI:10.1016/j.amjcard.2009.02.025 · 3.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Weight loss has been shown to decrease liver fat content and whole-body insulin resistance. The current study was conducted to investigate the simultaneous effects of rapid weight reduction with a very-low-calorie diet on liver glucose and fatty acid metabolism and liver adiposity.
We hypothesized that liver insulin resistance and free fatty acid uptake would decrease after weight loss and that they are associated with reduction of liver fat content.
Thirty-four healthy obese subjects (body mass index, 33.7 +/- 8.0 kg/m(2)) were studied before and after a very-low-calorie diet for 6 wk. Hepatic glucose uptake and endogenous glucose production were measured with [(18)F]fluorodeoxyglucose during hyperinsulinemic euglycemia and fasting hepatic fatty acid uptake with [(18)F]fluoro-6-thia-heptadecanoic acid and positron emission tomography. Liver volume and fat content were measured using magnetic resonance imaging and spectroscopy.
Subjects lost weight (11.2 +/- 2.9 kg; P < 0.0001). Liver volume decreased by 11% (P < 0.002), which was partly explained by decreased liver fat content (P < 0.0001). Liver free fatty acid uptake was 26% lower after weight loss (P < 0.003) and correlated with the decrement in liver fat content (r = 0.54; P < 0.03). Hepatic glucose uptake during insulin stimulation was unchanged, but the endogenous glucose production decreased by 40% (P < 0.04), and hepatic insulin resistance by 40% (P < 0.05).
The liver responds to a 6-wk period of calorie restriction with a parallel reduction in lipid uptake and storage, accompanied by enhancement of hepatic insulin sensitivity and clearance.