1. |
- Fryklund, Claes, et al.
(author)
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Impaired glucose transport in inguinal adipocytes after short-term high-sucrose feeding in mice
- 2020
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In: Journal of Nutritional Biochemistry. - : Elsevier BV. - 0955-2863. ; 78
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Journal article (peer-reviewed)abstract
- Diets enriched in sucrose severely impair metabolic regulation and are associated with obesity, insulin resistance and glucose intolerance. In the current study, we investigated the effect of 4 weeks high-sucrose diet (HSD) feeding in C57BL6/J mice, with specific focus on adipocyte function. Mice fed HSD had slightly increased adipose tissue mass but displayed similar hepatic triglycerides, glucose and insulin levels, and glucose clearance capacity as chow-fed mice. Interestingly, we found adipose depot-specific differences, where both the non- and insulin-stimulated glucose transports were markedly impaired in primary adipocytes isolated from the inguinal fat depot from HSD-fed mice. This was accompanied by decreased protein levels of both GLUT4 and AS160. A similar but much less pronounced trend was observed in the retroperitoneal depot. In contrast, both GLUT4 expression and insulin-stimulated glucose uptake were preserved in adipocytes isolated from epididymal adipose tissue with HSD. Further, we found a slight shift in cell size distribution towards larger cells with HSD and a significant decrease of ACC and PGC-1α expression in the inguinal adipose tissue depot. Moreover, fructose alone was sufficient to decrease GLUT4 expression in cultured, mature adipocytes. Altogether, we demonstrate that short-term HSD feeding has deleterious impact on insulin response and glucose transport in the inguinal adipose tissue depot, specifically. These changes occur before the onset of systemic glucose dysmetabolism and therefore could provide a mechanistic link to overall impaired energy metabolism reported after prolonged HSD feeding, alone or in combination with HFD.
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2. |
- Hansson, Björn, et al.
(author)
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A hypothesis for insulin resistance in primary human adipocytes involving MRTF-A and suppression of PPARγ
- 2020
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In: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 0006-291X. ; 533:1, s. 64-69
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Journal article (peer-reviewed)abstract
- Obesity is the main risk factor behind insulin resistance and type 2 diabetes. Still, the mechanism behind adipocyte dysfunction is not yet resolved. Recently, we reported that rapid actin remodeling correlates with adipose cell size changes after short-term overfeeding. Therefore, we hypothesized that the actin-driven myocardin-related transcription factor (MRTF-A) contributes to impaired mature adipocyte function. Primary human adipocytes were subjected to adenoviral overexpression of MRTF-A or MRTF-B, followed by Western blot analysis and tracer glucose uptake assay. Further, we assessed cell size distribution, insulin response, MRTF-A localization, actin organization and degree of polymerization in adipocytes isolated from Ob/Ob mice. Overexpression of MRTF-A, but not MRTF-B, markedly suppressed PPARγ expression. Further, MRTF-A expression resulted in decreased IRS-1 level, shifted phosphorylation of Akt (pS473/pT308), IRS-1 (pS302) and AS160 (pT642), and lowered insulin-stimulated glucose uptake. Hypertrophic adipocytes from Ob/Ob mice displayed an increased proportion of polymerized actin, and increased nuclear translocation of MRTF-A compared with control (Ob/+). Similar with human adipocytes overexpressing MRTF-A, adipocytes isolated from Ob/Ob mice had reduced expression of IRS-1 and PPARγ, as well as impaired insulin response. Together, these data demonstrate that MRTF-A negatively influences insulin sensitivity and the expression of key targets in fully mature human adipocytes. This suggests that MRTF-A is poised to exert a transcriptional response in hypertrophic adipocytes, contributing to adipocyte dysfunction and insulin resistance.
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3. |
- Morén, Björn, et al.
(author)
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Surface-associated lipid droplets : an intermediate site for lipid transport in human adipocytes?
- 2020
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In: Adipocyte. - : Informa UK Limited. - 2162-3945 .- 2162-397X. ; 9:1, s. 636-648
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Journal article (peer-reviewed)abstract
- Adipose tissue plays a major role in regulating whole-body energy metabolism. While the biochemical processes regulating storage and release of excess energy are well known, the temporal organization of these events is much less defined. In this study, we have characterized the presence of small surface-associated lipid droplets, distinct from the central droplet, in primary human adipocytes. Based on microscopy analyses, we illustrate the distribution of mitochondria, endoplasmic reticulum and lysosomes in the vicinity of these specialized lipid droplets. Ultrastructure analysis confirmed the presence of small droplets in intact adipose tissue. Further, CIDEC, known to bind and regulate lipid droplet expansion, clearly localized at these lipid droplets. Neither acute or prolonged stimulation with insulin or isoprenaline, or pharmacologic intervention to suppress lipid flux, affected the presence of these lipid droplets. Still, phosphorylated perilipin and hormone-sensitive lipase accumulated at these droplets following adrenergic stimuli, which supports metabolic activity at these locations. Altogether, we propose these lipid droplet clusters represent an intermediate site involved in lipid transport in primary adipocytes.
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