| 1. |
|
|
| 2. |
|
|
| 3. |
- Bickerton, A. S. T., et al.
(författare)
-
Adipose tissue fatty acid metabolism in insulin-resistant men
- 2008
-
Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 51:8, s. 1466-1474
-
Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis Increased NEFA production and concentrations may underlie insulin resistance. We examined systemic and adipose tissue NEFA metabolism in insulin-resistant overweight men (BM1 25-35 kg/m(2)). Methods In a cohort study we examined NEFA concentrations in men in the upper quartile of fasting insulin (n = 124) and in men with fasting insulin below the median (n 159). In a metabolic study we examined NEFA metabolism in the fasting and postprandial states, in ten insulin-resistant men and ten controls. Results In the cohort study, fasting NEFA concentrations were not significantly different between the two groups (median values: insulin-resistant men, 410 mu mol/l; controls, 445 2 mu mol/l). However, triacylglycerol concentrations differed markedly (1.84 vs 1.18 mmol/l respectively, p<0.001). In the metabolic study, arterial NEFA concentrations again did not differ between groups, whereas triacylglycerol concentrations were significantly higher in insulin-resistant men. Systemic NEFA production and the release of NEFA from subcutaneous adipose tissue, expressed per unit of fat mass, were both reduced in insulin-resistant men compared with controls (fasting values by 32%, p=0.02, and 44%, p=0.04 respectively). 3-Hydroxybutyrate concentrations, an index of hepatic fat oxidation and ketogenesis, were lower (p=0.03). Conclusions/interpretation Adipose tissue NEFA output is not increased (per unit weight of tissue) in insulin resistance. On the contrary, it appears to be suppressed by high fasting insulin concentrations. Alterations in triacylglycerol metabolism are more marked than those in NEFA metabolism. and are indicative of altered metabolic partitioning of fatty acids (decreased oxidation, increased esterification) in the liver.
|
|
| 4. |
- Risérus, Ulf, et al.
(författare)
-
Activation of peroxisome proliferator-activated receptor (PPAR)delta promotes reversal of multiple metabolic abnormalities, reduces oxidative stress, and increases fatty acid oxidation in moderately obese men
- 2008
-
Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 57:2, s. 332-339
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIEVE-Pharmacological use of peroxisome proliferator-activated receptor (PPAR)delta agonists and transgenic overexpression of PPAR delta in mice suggest amelioration of features of the metabolic syndrome through enhanced fat oxidation in skeletal muscle. We hypothesize a similar mechanism operates in humans. RESEARCH DESIGN AND METHODS-The PPAR delta agonist (10 mg o.d. GW501516), a comparator PPAR alpha agonist (20 mu g o.d. GW590735)), and placebo were given in a double-blind, randomized, three-parallel group, 2-week study to six healthy moderately overweight subjects in each group. Metabolic evaluation was made before and after treatment including liver fat quantification, fasting blood samples, a 6-h meal tolerance test with stable isotope fatty acids, skeletal muscle biopsy for gene expression, and urinary isoprostanes for global oxidative stress. RESULTS-Treatment with GW501516 showed statistically significant reductions in fasting plasma triglycerides (-30%), apolipoprotein B (-26%), LDL cholesterol (-23%), and insulin (-11%), whereas HDL cholesterol was unchanged. A 20% reduction in liver fat content (P < 0.05) and 30% reduction in urinary isoprostanes (P = 0.01) were also observed. Except for a lowering of triglycerides (-30%, P < 0.05), none of these changes were observed in response to GW590735. The relative proportion of exhaled CO, directly originating from the fat content of the meal was increased (P < 0.05) in response to GW501516, and skeletal muscle expression of carnitine palmitoyl-transferase 1b (CPT1b) was also significantly increased. CONCLUSIONS-The PPAR delta agonist GW501516 reverses multiple abnormalities associated with the metabolic syndrome without increasing oxidative stress. The effect is probably caused by increased fat oxidation in skeletal muscle.
|
|
| 5. |
- Ruge, Toralph, et al.
(författare)
-
Fasted to fed trafficking of fatty acids in human adipose tissue reveals a novel regulatory step for enhanced fat storage.
- 2009
-
Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X.
-
Tidskriftsartikel (refereegranskat)abstract
- Context: Absence or excess of adipose tissue are both associated with metabolic complications implying the importance of well-functioning adipose tissue present in normal amounts. Adipose tissue sequesters dietary fat and thus protects other tissues from excess fat exposure, especially following meals. Objective: Use of an integrative physiological technique to quantify trafficking of fatty acids (FA) in adipose tissue over a 24-h period. Methods: Adipose tissue FA handling was studied in response to three meals in eight healthy men by the combination of arterio-venous blood sampling, tissue blood flow, and specific labelling of FA tracing of exogenous and endogenous fat by stable isotope methodology. Results: The efficiency of adipose tissue FA uptake increased robustly with each meal. Chylomicron-triglyceride (TG) was the dominating source of FA. Adipose tissue fractional extraction of chylomicron-TG increased from 21+/-4 to 47+/-8% (p=0.03) between the first and last meal. Although adipose tissue lipoprotein lipase (LPL) action increased with time (2-fold), there was an even greater increase in FA re-esterification (3-fold), which led to a reduced spillover of chylomicron-derived FA, from 77+/-15 to 34+/-7% (p=0.04) comparing the end of the first and the third meal period. Increased uptake of VLDL-derived FA was observed, but spillover of VLDL-derived FA was only seen in the fasting state. Conclusion: Human adipose tissue has a significant potential to up-regulate fat storage during a normal day that goes beyond increased LPL activation. The adaptation towards increasing fat storage may provide an explanation for the beneficial properties of normal amounts of adipose tissue.
|
|
