| 1. |
- Cancello, Raffaella, et al.
(författare)
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Reduction of macrophage infiltration and chemoattractant gene expression changes in white adipose tissue of morbidly obese subjects after surgery-induced weight loss.
- 2005
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Ingår i: Diabetes. - 0012-1797. ; 54:8, s. 2277-86
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Tidskriftsartikel (refereegranskat)abstract
- In human obesity, the stroma vascular fraction (SVF) of white adipose tissue (WAT) is enriched in macrophages. These cells may contribute to low-grade inflammation and to its metabolic complications. Little is known about the effect of weight loss on macrophages and genes involved in macrophage attraction. We examined subcutaneous WAT (scWAT) of 7 lean and 17 morbidly obese subjects before and 3 months after bypass surgery. Immunomorphological changes of the number of scWAT-infiltrating macrophages were evaluated, along with concomitant changes in expression of SVF-overexpressed genes. The number of scWAT-infiltrating macrophages before surgery was higher in obese than in lean subjects (HAM56+/CD68+; 22.6 +/- 4.3 vs. 1.4 +/- 0.6%, P < 0.001). Typical "crowns" of macrophages were observed around adipocytes. Drastic weight loss resulted in a significant decrease in macrophage number (-11.63 +/- 2.3%, P < 0.001), and remaining macrophages stained positive for the anti-inflammatory protein interleukin 10. Genes involved in macrophage attraction (monocyte chemotactic protein [MCP]-1, plasminogen activator urokinase receptor [PLAUR], and colony-stimulating factor [CSF]-3) and hypoxia (hypoxia-inducible factor-1alpha [HIF-1alpha]), expression of which increases in obesity and decreases after surgery, were predominantly expressed in the SVF. We show that improvement of the inflammatory profile after weight loss is related to a reduced number of macrophages in scWAT. MCP-1, PLAUR, CSF-3, and HIF-1alpha may play roles in the attraction of macrophages in scWAT.
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| 2. |
- Luukkonen, Panu K., et al.
(författare)
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Saturated fat is more metabolically harmful for the human liver than unsaturated fat or simple sugars
- 2018
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 41:8, s. 1732-1739
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Nonalcoholic fatty liver disease (i.e., increased intrahepatic triglyceride [IHTG] content), predisposes to type 2 diabetes and cardiovascular disease. Adipose tissue lipolysis and hepatic de novo lipogenesis (DNL) are the main pathways contributing to IHTG. We hypothesized that dietary macronutrient composition influences the pathways, mediators, and magnitude of weight gain-induced changes in IHTG. RESEARCH DESIGN AND METHODS: We overfed 38 overweight subjects (age 48 ± 2 years, BMI 31 ± 1 kg/m2, liver fat 4.7 ± 0.9%) 1,000 extra kcal/day of saturated (SAT) or unsaturated (UNSAT) fat or simple sugars (CARB) for 3 weeks. We measured IHTG (1H-MRS), pathways contributing to IHTG (lipolysis ([2H5]glycerol) and DNL (2H2O) basally and during euglycemic hyperinsulinemia), insulin resistance, endotoxemia, plasma ceramides, and adipose tissue gene expression at 0 and 3 weeks. RESULTS: Overfeeding SAT increased IHTG more (+55%) than UNSAT (+15%, P < 0.05). CARB increased IHTG (+33%) by stimulating DNL (+98%). SAT significantly increased while UNSAT decreased lipolysis. SAT induced insulin resistance and endotoxemia and significantly increased multiple plasma ceramides. The diets had distinct effects on adipose tissue gene expression. CONCLUSIONS: Macronutrient composition of excess energy influences pathways of IHTG: CARB increases DNL, while SAT increases and UNSAT decreases lipolysis. SAT induced the greatest increase in IHTG, insulin resistance, and harmful ceramides. Decreased intakes of SAT could be beneficial in reducing IHTG and the associated risk of diabetes. © 2018 by the American Diabetes Association.
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| 3. |
- Voland, Lise, et al.
(författare)
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Tissue pleiotropic effect of biotin and prebiotic supplementation in established obesity
- 2023
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Ingår i: American Journal of Physiology. Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 325:4, s. E390-E405
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Tidskriftsartikel (refereegranskat)abstract
- Combination therapies targeting multiple organs and metabolic pathways are promising therapeutic options to combat obesity progression and/or its comorbidities. The alterations in the composition of the gut microbiota initially observed in obesity have been extended recently to functional alterations. Bacterial functions involve metabolite synthesis that may contribute to both the gut microbiota and the host physiology. Among them are B vitamins, whose metabolism at the systemic, tissue, or microbial level is dysfunctional in obesity. We previously reported that the combination of oral supplementation of a prebiotic (fructo-oligosaccharides, FOS) and vitamin B7/B8 (biotin) impedes fat mass accumulation and hyperglycemia in mice with established obesity. This was associated with an attenuation of dysbiosis with improved microbial vitamin metabolism. We now extend this study by characterizing whole body energy metabolism along with adipose tissue transcriptome and histology in this mouse model. We observed that FOS resulted in increased caloric excretion in parallel with downregulation of genes and proteins involved in jejunal lipid transport. The combined treatments also strongly inhibited the accumulation of subcutaneous fat mass, with a reduced adipocyte size and expression of lipid metabolism genes. Downregulation of inflammatory and fibrotic genes and proteins was also observed in both visceral and brown adipose tissues and liver by combined FOS and biotin supplementation. In conclusion, oral administration of a prebiotic and biotin has a beneficial impact on the metabolism of key organs involved in the pathophysiology of obesity, which could have promising translational applications.
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