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Biomedical subjects

P Schrauwen

Publications and source records attributed to P Schrauwen.

At least 19 recordsLinked to original sources
PubMed2006

Impaired in vivo mitochondrial function but similar intramyocellular lipid content in patients with type 2 diabetes mellitus and BMI-matched control subjects.

AIMS/HYPOTHESIS: Mitochondrial dysfunction and increased intramyocellular lipid (IMCL) content have both been implicated in the development of insulin resistance and type 2 diabetes mellitus, but the relative contributions of these two factors in the aetiology of diabetes are unknown. As obesity is an independent determinant of IMCL content, we examined mitochondrial function and IMCL content in overweight type 2 diabetes patients and BMI-matched normoglycaemic controls. METHODS: In 12 overweight type 2 diabetes patients and nine controls with similar BMI (29.4 +/- 1 and 29.3 +/- 0.9 kg/m(2) respectively) in vivo mitochondrial function was determined by measuring phosphocreatine recovery half-time (PCr half-time) immediately after exercise, using phosphorus-31 magnetic resonance spectroscopy. IMCL content was determined by proton magnetic resonance spectroscopic imaging and insulin sensitivity was measured with a hyperinsulinaemic-euglycaemic clamp. RESULTS: The PCr half-time was 45% longer in diabetic patients compared with controls (27.3 +/- 3.5 vs 18.7 +/- 0.9 s, p < 0.05), whereas IMCL content was similar (1.37 +/- 0.30 vs 1.25 +/- 0.22% of the water resonance), and insulin sensitivity was reduced in type 2 diabetes patients (26.0 +/- 2.2 vs 18.9 +/- 2.3 mumol min(-1) kg(-1), p < 0.05 [all mean +/- SEM]). PCr half-time correlated positively with fasting plasma glucose (r (2) = 0.42, p < 0.01) and HbA(1c) (r (2) = 0.48, p < 0.05) in diabetic patients. CONCLUSIONS/INTERPRETATION: The finding that in vivo mitochondrial function is decreased in type 2 diabetes patients compared with controls whereas IMCL content is similar suggests that low mitochondrial function is more strongly associated with insulin resistance and type 2 diabetes than a high IMCL content per se. Whether low mitochondrial function is a cause or consequence of the disease remains to be investigated.

Aged↗
PubMed2006

Peroxisome proliferator-activated receptor-gamma coactivator-1 and insulin resistance: acute effect of fatty acids.

AIMS/HYPOTHESIS: Peroxisome proliferator-activated receptor (PPAR)-gamma coactivator-1 (PPARGC1), a coactivator regulating the transcription of genes involved in oxidative metabolism, is downregulated in patients with type 2 diabetes and in their first-degree relatives. Whether this downregulation is a cause or effect of early aberrations in the development of insulin resistance, such as disturbances in fat metabolism, is unknown. We examined whether lipid-induced insulin resistance was associated with downregulation of expression of skeletal muscle genes involved in oxidative metabolism and mitochondrial biogenesis in humans. MATERIALS AND METHODS: Nine healthy lean male subjects underwent a 6-h hyperinsulinaemic-euglycaemic clamp with simultaneous infusion of either a lipid emulsion or glycerol as a control. Blood was sampled at regular time points and muscle biopsies were taken before and after every test. Intramuscular triacylglycerol (IMTG) content was determined by Oil Red O staining and gene expression was measured by quantitative PCR. RESULTS: Lipid infusion resulted in a approximately 2.7-fold increase in plasma NEFA levels and a 31+/-6% decrease in insulin sensitivity (p=0.001). The infusion of lipids resulted in a approximately 1.6-fold increase in IMTG (p=0.02), whereas during the clamp with glycerol infusion IMTG tended to decrease to approximately 53% of preinfusion levels (p=0.065). Lipid infusion decreased PPARGC1A, PPARGC1B and PPARA expression to approximately 61, 77 and approximately 52% of basal values respectively, whereas expression of uncoupling protein 3 was upregulated 1.8-fold (all p<0.05). CONCLUSIONS/INTERPRETATION: Acute elevation of plasma NEFA levels, leading to muscular fat accumulation and insulin resistance, downregulates PPARGC1A, PPARGC1B and PPARA expression, suggesting that the decrease in PPARGC1 expression observed in the (pre)diabetic state may be the result, rather than the cause of lipid-induced insulin resistance.

Adult↗
PubMed2006

Short-term training is accompanied by a down regulation of ACC2 mRNA in skeletal muscle.

Recently, we showed that short-term training induced a rapid increase in IMCL whilst insulin sensitivity tended to improve. Here we investigate molecular adaptations accompanying this physiological training-induced accumulation of IMCL. Nine untrained men (age: 23.3 +/- 3.2 y; maximal power output: 3.8 +/- 0.6 W/kg body weight) trained for two weeks. Before and after training, subjects cycled for three hours and biopsies were taken before and after exercise. mRNA concentrations of ACC2, HSL, LPL, Glut4 and HKII were quantified by RT-PCR and association of Glut4 with the membrane was quantified by immunohistochemical method. Endurance training resulted in a decrease of 29.1 % in ACC2 mRNA (p = 0.02). After training, ACC2 mRNA tended to decrease with acute exercise (- 24.4 % [p = 0.06]). HSL mRNA decreased with acute exercise after training (- 37.3 % [p = 0.002]). LPL mRNA concentrations increased with acute exercise before training (+ 42.4 % [p = 0.05]) and HKII mRNA increased with acute exercise before (+ 72.5 % [p = 0.025]) and after training (+ 99.3 % [p = 0.05]). After acute exercise, more Glut4 was associated with the membrane than before exercise, but it was not affected by training. We conclude that the training-induced increase in IMCL was accompanied by molecular adaptations in muscle to improve fat oxidative capacity, while markers of glucose metabolism were not yet changed. The present data are in line with the hypothesis that the fat oxidative capacity might be more important than the IMCL content in determining insulin sensitivity.

Acetyl-CoA Carboxylase↗
PubMed2006

PPARgamma activity in subcutaneous abdominal fat tissue and fat mass gain during short-term overfeeding.

OBJECTIVE: As the peroxisome proliferator-activated receptor gamma (PPARgamma) plays a central role in fat mass regulation, we investigated whether initial subcutaneous PPARgamma activity is related to fat mass generation during overfeeding. SUBJECTS: Fourteen healthy female subjects (age 25 +/- 4 years, BMI 22.1 +/- 2.3 kg/m2). DESIGN AND MEASUREMENTS: Subjects were overfed with a diet supplying 50% more energy than baseline energy requirements for 14 days. Fasting blood samples were analyzed for leptin, insulin and glucose. Fasting subcutaneous abdominal fat biopsies were obtained for analysis of PPARgamma1, PPARgamma2, aP2 and UCP2 mRNAs. RESULTS: Initial PPARgamma1 and 2, aP2 and UCP2 mRNAs were not related to fat gain (P > 0.12). However, PPARgamma1, PPARgamma2 and aP2 mRNA changes were positively related to changes in plasma leptin (P < 0.05) and, except aP2 (P = 0.06), to fat gain (P < 0.05). PPARgamma and aP2 mRNA changes were positively related (P<0.01), indicating that PPARgamma mRNA levels reflected PPARgamma activity. CONCLUSION: These data suggest that the ability to increase PPARgamma activity might be involved in the susceptibility to gain weight during a positive energy balance.

Adipogenesis↗
PubMed2005

Acylation-stimulating protein: effect of acute exercise and endurance training.

INTRODUCTION: Acylation-stimulating protein (ASP) is an adipocyte-derived protein that contributes to fatty acid clearance. Regular exercise training improves fatty acid handling. OBJECTIVE: To examine the effect of acute exercise and short-term endurance training on ASP levels. SUBJECTS: Eight untrained men (age: 23.5+/-3.4 y; maximal power output (Wmax): 3.7+/-0.6 W/kg body weight). DESIGN: Subjects were trained for 2 weeks. Before and after training, blood was sampled during a 3-h exercise test, and insulin sensitivity was assessed by an insulin tolerance test. RESULTS: Before training, ASP levels decreased during exercise (from 17.9+/-2.9 to 15.5+/-3.7 nmol/l at t=0 vs 180, P<0.05). Endurance training decreased fasting ASP levels significantly (17.9+/-2.9 vs 13.4+/-2.3 nmol/l pre- and post-training, P<0.001). Interestingly, after 2 weeks of endurance training, ASP levels tended to increase during exercise (from 13.4+/-2.3 to 17.2+/-4.5 nmol/l at t=0 vs 180, P=0.09). Baseline ASP levels correlated negatively with insulin sensitivity both before (r=-0.86, P<0.01) and after training (r=-0.82, P<0.05). CONCLUSION: Short-term endurance training reduces baseline ASP levels. These data fit with the hypothesis that reduced ASP levels indicate improved ASP sensitivity.

Adult↗
PubMed2005

Towards comprehension of the physiological role of UCP3.

Thyroid hormones have long been known to stimulate energy expenditure partly via loss of metabolic efficiency. The mechanism underlying the loss in metabolic efficiency observed, however, is not yet understood. An important candidate gene responsible for thyroid hormone induced thermogenesis was identified in 1997 with the discovery of skeletal muscle-uncoupling protein 3 (UCP3), a protein with approximately 60 % homology to the brown adipose tissue uncoupling protein 1 (UCP1). This short review summarizes our presentation held at the 'Thyroid and Sports' meeting; it does not aim to provide a concise overview of the available literature at this topic. Although induction of the UCP3 gene and increased protein expression during hyperthyroidism has been shown, there are no convincing data that increased UCP3 levels account for the increase in thermogenesis in the hyperthyroid state in humans. In contrast to cell and animal studies using ectopic overexpression of UCP3 as a model, induction of UCP3 in humans does not result in any apparent mitochondrial uncoupling. Hence, the primary physiological role of UCP3 may not be mitochondrial uncoupling, but uncoupling may occur as a side effect of a more pivotal role played by UCP3. Recently, UCP3 has been hypothesized to export fatty acid anions and/or lipid peroxides away from the mitochondrial matrix to prevent mitochondria from the harmful effects of peroxidized lipids. The present review aims to provide an overview of studies testing the feasibility of this unconventional function of UCP3.

Adipose Tissue↗
PubMed2005

Effect of 2 weeks of endurance training on uncoupling protein 3 content in untrained human subjects.

AIM: The mitochondrial uncoupling protein-3 (UCP3) is able to lower the proton gradient across the inner mitochondrial membrane, thereby uncoupling substrate oxidation from ATP production and dissipating energy as heat. What the effect of endurance training on UCP3 is, is still controversial. Endurance-trained athletes are characterized by lower levels of UCP3, but longitudinal studies in rodents reported no effect of endurance training on muscular UCP3 levels. Here, we examined the effect of a 2-week training programme on skeletal muscle UCP3 protein content in untrained human subjects, and hypothesized that UCP3 will be reduced after the training programme. METHODS: Nine untrained men [age: 23.3 +/- 3.2 years; BMI: 22.6 +/- 2.6 kg m(-2); maximal power output (W(max)): 3.8 +/- 0.6 W kg(-1) body weight] trained for 2 weeks. Before and at least 72 h after the training period, muscle biopsies were taken for determination of UCP3 protein content. RESULTS: UCP3 protein content tended to be lower after the training programme [95 +/- 10 vs. 109 +/- 12 arbitrary units (AU), P = 0.08]. Cytochrome c content tended to increase with 33% in response to endurance training (52 +/- 6 vs. 39 +/- 6 AU, P = 0.08). The ratio UCP3 relative to cytochrome c tended to decrease significantly upon endurance training (2.0 +/- 0.4 vs. 3.2 +/- 0.6 AU, P = 0.01). CONCLUSION: A short-term (2-week) endurance training programme decreased UCP3 protein levels and significantly reduced the ratio of UCP3 to cytochrome c.

Adult↗
PubMed2004

Improved glucose homeostasis in mice overexpressing human UCP3: a role for AMP-kinase?

OBJECTIVE: An unexplained phenotype of mice overexpressing human UCP3 is their improved glucose homeostasis. Since overexpression of UCP3 might affect the energy charge of the cell, we investigated whether these mice have an increased AMP-activated protein kinase (AMPK) activity. METHODS: Mitochondrial localisation of UCP3 was determined by immunoelectronmicroscopy and AMPK activity was measured in medial gastrocnemius of control mice and mice overexpressing human UCP3. RESULTS: Mice overexpressing human UCP3 had 5.8 fold higher levels of UCP3 protein, for which mitochondrial localisation was confirmed by immunoelectronmicroscopy. The ATP/AMP ratio was significantly lower in mice over-expressing UCP3 compared to the wild-type (10.9+/-1.6 vs 20.4+/-1.9 AU, P=0.03). Over-expression of UCP3 resulted in increased AMPK alpha1 activity (1.23+/-0.05 vs 1.00+/-0.06 normalized values, P=0.004) and a tendency towards increased AMPK alpha2 activity (1.18+/-0.08 vs 1.00+/-0.10 normalized values, P=0.08). CONCLUSION: Increased AMPK activity provides a plausible explanation for the improved glucose tolerance characteristic for these mice.

Adenine Nucleotides↗
PubMed2004

Substrate oxidation differences between high- and low-intensity exercise are compensated over 24 hours in obese men.

OBJECTIVE: Exercise has been proposed as a tool for the prevention of obesity. Apart from an effect on energy expenditure, in particular low-intensity (LI) exercise might also influence substrate metabolism in favour of fat oxidation. It is however unclear what is the most beneficial exercise regime for obese people. We therefore studied the effect of either high-intensity (HI) or LI exercise on 24 h energy expenditure (24 h EE) and substrate metabolism. METHODS: Eight healthy obese male volunteers (age: 38+/-1 y, BMI: 31+/-1 kg/m(2), W(max): 235+/-16 W) stayed in the respiration chamber for two nights and the day in-between. In the chamber they cycled either at a HI (three times 30 min in a interval protocol (2.5 min 80/50% W(max))) or LI (three times 60 min continuously at 38% W(max)) protocol with an equicaloric energy expenditure. In the chamber subjects were fed in energy balance (37/48/15% of energy as fat/carbohydrate/protein). RESULTS: The 24 h EE was not significantly different between protocols. In both protocols, sleeping metabolic rate (SMR) was elevated after the exercise (average+6.7%). The 24 h respiratory quotient (24 h RQ) was not different between protocols. During exercise, RQ was higher in the HI compared to the LI protocol (0.93 vs 0.91 resp., P<0.05), whereas in the postexercise period RQ tended to be lower in the HI compared to the LI protocol (P=0.06). CONCLUSION: 24 h EE is not differently affected by HI or LI exercise in obese men. Similarly, the differences in HI and LI exercise, RQ are compensated postexercise leading to similar substrate oxidation patterns over 24 h independently of the level of exercise intensity.

Adult↗
PubMed2003

Uncoupling protein-3 content is decreased in peripheral skeletal muscle of patients with COPD.

Mechanical efficiency is reduced in patients with chronic obstructive pulmonary disease (COPD). Furthermore, altered fibre-type distribution and metabolic profile has been observed in peripheral skeletal muscle of COPD patients. Since skeletal muscular uncoupling protein-3 (UCP3) has been implicated in the regulation of energy metabolism, the aim of this study was to assess UCP3 in peripheral skeletal muscle of COPD patients and healthy controls. A total of 16 COPD patients and 11 healthy age-matched control subjects were studied. Mechanical efficiency was measured by means of cycle ergometry. Biopsies were taken from the vastus lateralis, and UCP3 and cytochrome c (as a marker for mitochondrial content) levels were assessed by Western blotting. Muscle fibre types and metabolic profile were examined histochemically. UCP3 levels were markedly decreased in COPD compared to controls. In COPD patients, there was a positive correlation between UCP3 content and the forced expiratory volume in one second. UCP3 content was not related to mechanical efficiency, or other muscular data such as fibre types, markers of oxidative/glycolytic energy metabolism or cytochrome c. The authors of this study conclude that uncoupling protein-3 content is decreased in peripheral skeletal muscle of patients with chronic obstructive pulmonary disease and is related to disease severity, but not to mechanical efficiency. The low uncoupling protein-3 content is independent of the loss of oxidative capacity observed in these patients.

Aged↗
PubMed2003

The increase in intramyocellular lipid content is a very early response to training.

The present study investigated the influences of a 2-wk training program on intramyocellular lipid (IMCL) content, IMCL decrease during exercise, fat oxidation, and insulin sensitivity. Nine untrained men (age, 23.3 +/- 3.2 yr; body mass index, 22.6 +/- 2.6 kg/m(2); maximal power output, 3.8 +/- 0.6 W/kg body weight) trained for 2 wk. Before and after training, subjects cycled for 3 h while substrate oxidation was measured. IMCL content in the vastus lateralis muscle was determined before and after cycling by proton magnetic resonance spectroscopy. Before and after training, insulin sensitivity was assessed by an insulin tolerance test. The training period resulted in a significant increase in IMCL content by 42 +/- 14%. IMCL content decreased significantly during cycling. However, 2 wk of training were not sufficient to achieve increases in fat oxidation and/or use of IMCL during exercise. All markers used to test insulin sensitivity point toward improved insulin sensitivity, albeit not significant. We conclude that the increase in IMCL content is a very early response to training, preceding significant changes in insulin sensitivity. The results suggest that the presence of triglycerides alone does not necessarily have detrimental effects on insulin sensitivity. We confirm earlier reports that IMCL contributes to the energy used during prolonged submaximal exercise.

Adipose Tissue↗
PubMed2002

UCP3 protein expression is lower in type I, IIa and IIx muscle fiber types of endurance-trained compared to untrained subjects.

Uncoupling protein 3 (UCP3) is a muscle mitochondrial protein believed to uncouple the respiratory chain, producing heat and reducing aerobic ATP production. Our aim was to quantify and compare the UCP3 protein levels in type I, IIa and IIx skeletal muscle fibers of endurance-trained (Tr) and healthy untrained (UTr) individuals. UCP3 protein content was quantified using Western blot and immunofluorescence. Skeletal muscle fiber type was determined by both an enzymatic ATPase stain and immunofluorescence. UCP3 protein expression measured in skeletal muscle biopsies was 46% lower ( P=0.01) in the Tr compared to the UTr group. UCP3 protein expression in the different muscle fibers was expressed as follows; IIx>IIa>I in the fibers for both groups ( P<0.0167) but was lower in all fiber types of the Tr when compared to the UTr subjects ( P<0.001). Our results show that training status did not change the skeletal muscle fiber hierarchical UCP3 protein expression in the different fiber types. However, it affected UCP3 content more in type I and type IIa than in the type IIx muscle fibers. We suggest that this decrease may be in relation to the relative improvement in the antioxidant defense systems of the skeletal muscle fibers and that it might, as a consequence, participate in the training induced improvement in mechanical efficiency.

Adult↗
PubMed2002

Energy metabolism in humans at a lowered ambient temperature.

OBJECTIVE: Assessment of the effect of a lowered ambient temperature, ie 16 degrees C (61 degrees F), compared to 22 degrees C (72 degrees F), on energy intake (EI), energy expenditure (EE) and respiratory quotient (RQ) in men. DESIGN: Randomized within-subject design in which subjects stayed in a respiration chamber three times for 60 h each, once at 22 degrees C, and twice at 16 degrees C, wearing standardized clothing, executing a standardized daily activities protocol, and were fed in energy balance (EBI): no significant difference between EE and EI over 24 h). During the last 24 h at 22 degrees C, and once during the last 24 h at 16 degrees C, they were fed ad libitum. SUBJECTS: Nine dietary unrestrained male subjects (ages 24+/-5 y, body mass index (BMI) 22.7+/-2.1 kg/m(2), body weight 76.2+/-9.4 kg, height 1.83+/-0.06 m, 18+/-5% body fat). RESULTS: At 16 degrees C (EB), EE (total 24 h EE) was increased to 12.9+/-2.0 MJ/day as compared to 12.2+/-2.2 MJ/day at 22 degrees C (P<0.01). The increase was due to increases in sleeping metabolic rate (SMR; the lowest EE during three consecutive hours with hardly any movements as indicated by radar): 7.6+/-0.7 vs 7.2+/-0.7 MJ/day (P<0.05) and diet-induced thermogenesis (DIT; EE-SMR, when activity induced energy expenditure as indicated by radar=0): 1.7+/-0.4 vs 1.0+/-0.4 MJ/day (P<0.01). Physical activity level (PAL; EE/SMR) was 1.63-1.68. At 16 degrees C compared to at 22 degrees C, rectal, proximal and distal skin temperatures had decreased (P<0.01). RQ was not different between the two ambient temperature situations. During ad libitum feeding, subjects overate by 32+/-12% (at 22 degrees C) and by 34+/-14% (at 16 degrees C). Under these circumstances, the decrease of rectal temperature at 16 degrees C was attenuated, and inversely related to percentage overeating (r(2)=0.7; P<0.01). CONCLUSION: We conclude that at 16 degrees C, compared to 22 degrees C, energy metabolism was increased, due to increases in SMR and DIT. Overeating under ad libitum circumstances at 16 degrees C attenuated the decrease in rectal core body temperature.

Activities of Daily Living↗
PubMed2002

The effect of mild cold exposure on UCP3 mRNA expression and UCP3 protein content in humans.

OBJECTIVE: In rodents, adaptive thermogenesis in response to cold exposure and high-fat feeding is accomplished by the activation of the brown adipose tissue specific mitochondrial uncoupling protein, UCP1. The recently discovered human uncoupling protein 3 is a possible candidate for adaptive thermogenesis in humans. In the present study we examined the effect of mild cold exposure on the mRNA and protein expression of UCP3. SUBJECTS: Ten healthy male volunteers (age 24.4 +/- 1.6 y; height 1.83 +/- 0.02 m; weight 77.3 +/- 3.0 kg; percentage body fat 19 +/- 2). DESIGN: Subjects stayed twice in the respiration chamber for 60 h (20.00-8.00 h); once at 22 degrees C (72 degrees F), and once at 16 degrees C (61 degrees F). After leaving the respiration chamber, muscle biopsies were taken and RT-competitive-PCR and Western blotting was used to measure UCP3 mRNA and protein expression respectively. RESULTS: Twenty-four-hour energy expenditure was significantly increased at 16 degrees C compared to 22 degrees C (P<0.05). At 16 degrees C, UCP3T (4.6 +/- 1.0 vs 7.7 +/- 1.5 amol/microg RNA, P=0.07), UCP3L (2.0 +/- 0.5 vs 3.5 +/- 0.9 amol/microg RNA, P=0.1) and UCP3S (2.6 +/- 0.6 vs 4.2 +/- 0.7 amol/microg RNA, P=0.07) mRNA expression tended to be lower compared with at 22 degrees C, whereas UCP3 protein content was, on average, not different. However, the individual differences in UCP3 protein content (16-22 degrees C) correlated positively with the differences in 24 h energy expenditure (r=0.86, P<0.05). CONCLUSION: The present study suggests that UCP3 protein content is related to energy metabolism in humans and might help in the metabolic adaptation to cold exposure. However, the down-regulation of UCP3 mRNA with mild cold exposure suggests that prolonged cold exposure will lead to lower UCP3 protein content. What the function of such down-regulation of UCP3 could be is presently unknown.

Adult↗
PubMed2001

Fiber type dependent upregulation of human skeletal muscle UCP2 and UCP3 mRNA expression by high-fat diet.

OBJECTIVE: To test the hypothesis that consumption of a high-fat diet leads to an increase in UCP mRNA expression in human skeletal muscle. In a group of endurance athletes, with a range in fiber type distribution, we hypothesized that the effect of the high-fat diet on UCP2 and UCP3 mRNA expression is more pronounced in muscle fibers which are known to have a high capacity to shift from carbohydrate to fat oxidation (type IIA fibers). DESIGN: Ten healthy trained athletes (five males, five females) consumed a low-fat diet (17+/-0.9 en% of fat) and high-fat diet (41.4+/-1.4 en% fat) for 4 weeks, separated by a 4 week wash-out period. Muscle biopsies were collected at the end of both dietary periods. MEASUREMENTS: Using RT-PCR, levels of UCP2 and UCP3 mRNA expression were measured and the percentage of type I, IIA and IIB fibers were determined using the myofibrillar ATPase method in all subjects. RESULTS: UCP3L mRNA expression tended to be higher on the high-fat diet, an effect which reached significance when only males were considered (P=0.037). Furthermore, diet-induced change in mRNA expression of UCP3T (r: 0.66, P=0.037), UCP3L (r: 0.61, P=0.06) and UCP2 (r: 0.70, P=0.025), but not UCP3S, correlated significantly with percentage dietary fat on the high-fat diet. Plasma FFA levels were not different during the two diets. Finally, the percentage of type IIA fibers was positively correlated with the diet-induced change in mRNA expression for UCP2 (r: 0.7, P=0.03), UCP3L (r: 0.73, P=0.016) and UCP3T (r: 0.68, P=0.03) but not with UCP3S (r: 0.06, NS). CONCLUSION: UCP2 and UCP3 mRNAs are upregulated by a high-fat diet. This upregulation is more pronounced in humans with high proportions of type IIA fibers, suggesting a role for UCPs in lipid utilization.

Adult↗
PubMed2001

An alternative function for human uncoupling protein 3: protection of mitochondria against accumulation of nonesterified fatty acids inside the mitochondrial matrix.

The physiological function of the human uncoupling protein 3 UCP3, which was discovered in 1997, is unknown. Here we evaluate the available data on human UCP3 expression and show that UCP3 is up-regulated in situations where fatty acid delivery to the mitochondria exceeds oxidative capacity, whereas down-regulation of UCP3 is observed when oxidative capacity is enhanced. With a surplus of fatty acid delivery, accumulation of nonesterified fatty acids in the cytoplasm is likely to occur. Although the inner mitochondrial membrane provides a barrier for nonesterified fatty acids, neutral nonesterified fatty acids can partition into the phospholipid bilayer and flip-flop to the other side of the membrane, where they can be released into the mitochondrial matrix. Due to pH differences, these nonesterified fatty acids will be protonated. Because fatty acid anions can neither be metabolized inside the matrix or cross the inner mitochondrial membrane, accumulation of nonesterified fatty acids inside the matrix might occur. Therefore, we postulate that UCP3 is required for the outward translocation of fatty acids from the mitochondrial matrix. In this way, UCP3 is involved in the protection of mitochondria against accumulation of nonesterified fatty acids inside the mitochondrial matrix.

Animals↗
PubMed2001

Uncoupling protein 3 content is decreased in skeletal muscle of patients with type 2 diabetes.

Recently, a role for uncoupling protein-3 (UCP3) in carbohydrate metabolism and in type 2 diabetes has been suggested. Mice overexpressing UCP3 in skeletal muscle showed reduced fasting plasma glucose levels, improved glucose tolerance after an oral glucose load, and reduced fasting plasma insulin levels. However, data regarding the expression of UCP3 in patients with type 2 diabetes is inconsistent, and so far, there have been no reports of UCP3 protein content. Here we compared, for the first time, the protein levels of UCP3 in vastus lateralis muscle in 14 male type 2 diabetic patients (age 49.8 +/- 2.1 years; BMI 27.2 +/- 1.2 kg/m(2); mean +/- SE) with 16 male control subjects (age 48.0 +/- 1.9 years; BMI 23.4 +/- 0.6 kg/m(2)). We found that UCP3 protein levels were twice as low in patients with type 2 diabetes compared with control subjects (117 +/- 16 vs. 58 +/- 12 AU; P = 0.007). There was no correlation between UCP3 content and BMI. In conclusion, UCP3 content is lower in type 2 diabetic patients compared with healthy control subjects. These results are consistent with a role for UCP3 in glucose homeostasis and suggest a role for UCP3 in type 2 diabetes.

Blood Glucose↗