Acute in vivo effects of insulin on gene expression in adipose tissue in insulin-resistant and insulin-sensitive subjects

Westerbacka, Jukka; Corner, A. H.; Kannisto, Katja; Kolak, Maria; Makkonen, Janne; Korsheninnikova, Elena; Nyman, Tuulikki; Hamsten, Anders; Fisher, Rachel M.; Yki‐Järvinen, Hannele

doi:10.1007/s00125-005-0075-5

Cited by 50 publications

(49 citation statements)

References 90 publications

(114 reference statements)

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“…Overexpression of Adipoq in obese mice decreases infiltration of macrophages into AT and release of proinflammatory cytokines from adipocytes and stromal vascular cells [36]. In humans, gene expression of ADIPOQ in AT and circulating concentrations of adiponectin are decreased in obese and insulin-resistant compared with nonobese and insulin-sensitive individuals [32,37]. In keeping with such data, in the present study, the obese group had significantly lower gene expression of ADIPOQ in AT than the non-obese group.…”

Section: Discussionsupporting

confidence: 85%

Adipose tissue is inflamed in NAFLD due to obesity but not in NAFLD due to genetic variation in PNPLA3

et al. 2013

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Aims/hypothesis The rs738409 C>G single-nucleotide polymorphism in PNPLA3 leads to a missense mutation (I148M) which increases liver fat but does not cause insulin resistance. We hypothesised that patients with non-alcoholic fatty liver disease (NAFLD) due to the PNPLA3 variant ('PNPLA3 NAFLD'=PNPLA3-148MM) do not have adipose tissue (AT) inflammation in contrast with those with NAFLD due to obesity ('obese NAFLD'). Methods Biopsy specimens of AT were taken, and PNPLA3 genotype and liver fat ( 1 H-magnetic resonance spectroscopy) were determined in 82 volunteers, who were divided into groups based on either median BMI (obese 36.2± 0.7 kg/m 2 ; non-obese 26.0±0.4 kg/m 2 ) or PNPLA3 genotype. All groups were similar with respect to age and sex.The PNPLA3 subgroups were equally obese (PNPLA3-148MM, 31.1 ± 1.3 kg/m 2 ; PNPLA3-148II, 31.2 ± 0.8 kg/m 2 ), while the obese and non-obese subgroups had similar PNPLA3 genotype distribution. Gene expression of proinflammatory (MCP-1, CD68) and anti-inflammatory (Twist1, ADIPOQ) markers was measured using quantitative real-time RT-PCR. Results Liver fat was similarly increased in obese NAFLD (9.5±1.3% vs 5.1±0.9%, obese vs non-obese, p=0.007) and PNPLA3 NAFLD (11.4± 1.7% vs 5.3± 0.8%, PNPLA3-148MM vs PNPLA3-148II, p<0.001). Fasting serum insulin was higher in the obese than the non-obese group (76±6 vs 47±6 pmol/l, p<0.001), but similar in PNPLA3-148MM and PNPLA3-148II (60±8 vs 62±5 pmol/l, NS). In obese vs non-obese, MCP-1 and CD68 mRNAs were upregulated, whereas those of Twist1 and ADIPOQ were significantly downregulated. AT gene expression of MCP-1, CD68, Twist1 and ADIPOQ was similar in PNPLA3-148MM and PNPLA3-148II groups. Conclusions/interpretation PNPLA3 NAFLD is characterised by an increase in liver fat but no insulin resistance or AT inflammation, while obese NAFLD has all three of these features. Keywords

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Section: Discussionsupporting

confidence: 85%

Adipose tissue is inflamed in NAFLD due to obesity but not in NAFLD due to genetic variation in PNPLA3

et al. 2013

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“…Our study found that early insulin treatment significantly decreased IL-6 expression, which was inconsistent to a previous study, in which acute insulin infusion significantly stimulated the expression of IL-6, especially in insulin-resistant adipose tissue [10] . The discrepancies may be due to the different experimental procedures used (acute vs chronic).…”

Section: Wwwchinapharcom Chen X Et Alcontrasting

confidence: 99%

“…With insulin treatment, adiponectin expression was significantly increased in the obese mice. Our result is consistent with observation in other study [10] , in which mRNA concentration encoding adiponectin was increased significantly by acute euglycaemic hyperinsulinaemia in the insulin-sensitive adipose tissue. Insulin has also been reported to increase adiponectin secretion from omental but not subcutaneous adipocyte in human [18] .…”

Section: Wwwchinapharcom Chen X Et Alsupporting

confidence: 94%

“…Dysregulation of these hormones/adipokines is emerging as an important mechanism of systemic insulin resistance and metabolic disease [9] . Insulin infusion was shown to influence the secretion of adiponectin www.nature.com/aps Chen X et al Acta Pharmacologica Sinica npg and IL-6 [10] . The effect of insulin on visfatin expression in adipose tissue remains to be determined.…”

Section: Introductionmentioning

confidence: 99%

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Insulin therapy stimulates lipid synthesis and improves endocrine functions of adipocytes in dietary obese C57BL/6 mice

Chen

Zhu

et al. 2010

Acta Pharmacol Sin

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Aim: To evaluate whether insulin intervention could affect the metabolic and endocrine functions of adipose tissue. Methods: C57BL/6 mice were fed on a high-fat-diet for 12−16 weeks to induce insulin resistance. Insulin intervention was administered in the high-fat-diet mice for 4 weeks at 12 weeks (early insulin treatment) or 16 weeks (late insulin treatment). Intraperitoneal glucose tolerance tests were performed before and after insulin treatment. Expression levels of factors involved in the triglyceride synthesis and endocrine functions of adipose tissue including phosphoenolpyruvate carboxykinase (PEPCK-C), fatty acid synthase (FAS), aquaporin 7 (AQP7), adiponectin, visfatin, and interleukin-6 (IL-6) were determined by Western blot. Results: In the obese mice, glucose tolerance was impaired; triglyceride content was increased in the liver tissue; protein expression of FAS and adiponectin was decreased; expression of visfatin was increased in adipose tissue. After 4-week insulin treatment, glucose tolerance was improved; triglyceride content was decreased in the liver and skeletal muscle; expression of PEPCK-C, FAS, and adiponectin was increased in the adipose tissue; IL-6 and AQP7 expression was reduced in the fat. Early insulin treatment had better effect in increasing the expression of FAS and PEPCK-C and decreasing the expression of IL-6. Conclusion: These results indicate that insulin can target adipocytes for improvement of insulin sensitivity through stimulating triglyceride synthesis and partly improving endocrine functions.

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“…This difference in magnitude may be due to the insulin sensitivity, obesity status of subjects, as well as the subjects' ethnic origins. First, a recent study showed that the expression of key genes in the inflammatory pathways was higher in the insulin-resistant than in the insulin-sensitive groups (Westerbacka et al 2006). Secondly, a chronic systemic low-grade inflammation is typically observed in obese subjects.…”

Section: Gadd45bmentioning

confidence: 99%

Transcriptomic profiles of skeletal muscle tissue following an euglycemic-hyperinsulinemic clamp in insulin-resistant obese subjects

et al. 2012

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Insulin resistance in skeletal muscle is an early phenomenon in the pathogenesis of type 2 diabetes. Muscle is mainly responsible for insulin-stimulated glucose clearance from the bloodstream. Thus, regulation of gene expression in muscle tissue may be involved in the pathogenesis of insulin resistance. The objective was to investigate gene expression and metabolic pathways alterations in skeletal muscle tissue following an euglycemic-hyperinsulinemic clamp in obese insulin-resistant subjects. We carried out a transcriptome comparison of skeletal muscle tissue before and after a 3-h euglycemic-hyperinsulinemic clamp following 8-week supplementation with n-3 polyunsaturated fatty acid (PUFA) (1.8 g/day) with or without a supplement of fish gelatin (FG) (25 % of daily protein intake) in 16 obese insulin-resistant subjects. Results indicate that approximately 5 % (1932) of expressed transcripts were significantly changed after the clamp in both n-3 PUFA and n-3 PUFA ? FG supplementation periods. Of these differentially expressed transcripts, 1394 genes associated with enzymes, transcription and translation regulators, transporters, G protein-coupled receptors, cytokines, and ligand-dependent nuclear receptors were modified. Metabolic pathways that were significantly modified included liver X receptor/retinoid X receptors (RXR) activation, vitamin D receptor/RXR activation, interleukin (IL)-8, acute phase response, IL10, triggering receptor expressed on myeloid cells 1, peroxisome proliferatoractivated receptor, G-beta/gamma and hepatocyte growth factor and IL6 signaling. Taken together, results suggest that mainly inflammatory and transcription factors are modified following clamp in obese insulin-resistant subjects. Overall, understanding the changes in metabolic pathways due to insulin may be a potential target for the management of insulin resistance.

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Acute in vivo effects of insulin on gene expression in adipose tissue in insulin-resistant and insulin-sensitive subjects

Cited by 50 publications

References 90 publications

Adipose tissue is inflamed in NAFLD due to obesity but not in NAFLD due to genetic variation in PNPLA3

Adipose tissue is inflamed in NAFLD due to obesity but not in NAFLD due to genetic variation in PNPLA3

Insulin therapy stimulates lipid synthesis and improves endocrine functions of adipocytes in dietary obese C57BL/6 mice

Transcriptomic profiles of skeletal muscle tissue following an euglycemic-hyperinsulinemic clamp in insulin-resistant obese subjects

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