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. 2015 Aug;23(8):1616-24.
doi: 10.1002/oby.21139. Epub 2015 Jun 22.

Skeletal muscle interleukin-6 regulates metabolic factors in iWAT during HFD and exercise training

Jakob G Knudsen  1 , Laerke Bertholdt  1 , Ella Joensen  1 , Signe B Lassen  1 , Juan Hidalgo  2 , Henriette Pilegaard  1
Affiliations

Skeletal muscle interleukin-6 regulates metabolic factors in iWAT during HFD and exercise training

Jakob G Knudsen et al. Obesity (Silver Spring). 2015 Aug.

Abstract

Objective: To investigate the role of skeletal muscle (SkM) interleukin (IL)-6 in the regulation of adipose tissue metabolism.

Methods: Muscle-specific IL-6 knockout (IL-6 MKO) and IL-6(loxP/loxP) (Floxed) mice were subjected to standard rodent diet (Chow), high-fat diet (HFD), or HFD in combination with exercise training (HFD ExTr) for 16 weeks.

Results: Total fat mass increased (P < 0.05) in both genotypes with HFD. However, HFD IL-6 MKO mice had lower (P < 0.05) inguinal adipose tissue (iWAT) mass than HFD Floxed mice. Accordingly, iWAT glucose transporter 4 (GLUT4) protein content, 5'AMP activated protein kinase (AMPK)(Thr172) phosphorylation, and fatty acid synthase (FAS) mRNA content were lower (P < 0.05) in IL-6 MKO than Floxed mice on Chow. In addition, iWAT AMPK(Thr172) and hormone-sensitive lipase (HSL)(Ser565) phosphorylation as well as perilipin protein content was higher (P < 0.05) in HFD IL-6 MKO than HFD Floxed mice, and pyruvate dehydrogenase E1α (PDH-E1α) protein content was higher (P < 0.05) in HFD ExTr IL-6 MKO than HFD ExTr Floxed mice.

Conclusions: These findings indicate that SkM IL-6 affects iWAT mass through regulation of glucose uptake capacity as well as lipogenic and lipolytic factors.

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Figures

Figure 1
Figure 1
(a) Gel electrophoresis of PCR products generated with primers surrounding exon 2 of the IL‐6 gene in quadriceps (SkM), brown adipose tissue, heart, iWAT, eWAT, and liver and (b) IL‐6 mRNA content in quadriceps in Floxed and IL‐6 MKO mice after 16 weeks on Chow, HFD, or HFD combined with exercise training (HFD ExTr). A reduction in band size from 1,000 bp to 260 bp in panel a is consistent with loss of exon 2 of the IL‐6 gene. Values are mean ± SE. #Significantly different from Floxed within given intervention (P < 0.05).
Figure 2
Figure 2
Body weight, body composition, and food intake in Floxed and IL‐6 MKO mice after 16 weeks on Chow, HFD, or HFD combined with exercise training (HFD ExTr). (a) Body weight (n = 10), (b) lean mass as percentage of body weight (n = 4‐9), (c) fat mass as percentage of body weight (n = 4‐9), (d) iWAT mass (n = 10), (e) eWAT mass (n = 9‐10), (f) calorie intake (n = 10). Values are mean ± SE. *Significantly different from Chow within given genotype (P < 0.05). ¤Significantly different from HFD within given genotype (P < 0.05). #Significantly different from Floxed within given intervention (P < 0.05).
Figure 3
Figure 3
Whole‐body glucose metabolism and plasma NEFA in Floxed and IL‐6 MKO mice after 16 weeks on Chow, HFD, or HFD combined with exercise training (HFD ExTr). (a) Glucose tolerance calculated as glucose area under the curve (AUC), (b) insulin tolerance calculated as glucose AUC, and (c) plasma NEFA in Floxed mice and IL‐6 MKO mice (n = 7‐10). Values are mean ± SE. *Significantly different from Chow within given genotype (P < 0.05).
Figure 4
Figure 4
Regulation of AMPK and HSL in iWAT in Floxed and IL‐6 MKO mice after 16 weeks on Chow, HFD, or HFD combined with exercise training (HFD ExTr). (a) AMPKThr172 phosphorylation (phos), (b) HSLSer660 phos, (c) HSLSer565 phos, (d) AMPKα1 protein content, (e) HSL protein content, and (f) perilipin protein content (n = 9‐10). Values are mean ± SE. *Significantly different from Chow within given genotype (P < 0.05). ¤Significantly different from HFD within given genotype (P < 0.05). #Significantly different from Floxed within given intervention (P < 0.05).
Figure 5
Figure 5
Regulation of GLUT4 and PEPCK protein content as well as LPL and FAS mRNA content in Floxed and IL‐6 MKO mice after 16 weeks on Chow, HFD, or HFD combined with exercise training (HFD ExTr). (a) GLUT4 protein content, (b) PEPCK protein content, (c) LPL mRNA content, and (d) FAS mRNA content (n = 8‐10). Target mRNA is normalized to single‐stranded (ss) DNA. Values are mean ± SE. *Significantly different from Chow within given genotype (P < 0.05). #Significantly different from Floxed within given intervention (P < 0.05).
Figure 6
Figure 6
Regulation of PDH in Floxed and IL‐6 MKO mice after 16 weeks on Chow, HFD, or HFD combined with exercise training (HFD ExTr). (a) iWAT PDH‐E1αSer300 phosphorylation (phos), (b) PDH‐E1αSer232 phos, (c) PDK4 protein content and (d) PDH‐E1α protein content (n = 9‐10). Values are mean ± SE. *Significantly different from Chow within given genotype (P < 0.05). ¤Significantly different from HFD within given genotype (P < 0.05). #Significantly different from Floxed within given intervention (P < 0.05).
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References

    1. Scherer PE, Williams S, Fogliano M, Baldini G, Lodish HF. A novel serum protein similar to C1q, produced exclusively in adipocytes. J Biol Chem 1995;270:26746–26749. - PubMed
    1. Stallknecht B, Andersen PH, Vinten J, et al. Effect of physical training on glucose transporter protein and mRNA levels in rat adipocytes. Am J Physiol 1993; 265:E128–E34. - PubMed
    1. Hirshman MF, Goodyear LJ, Horton ED, Wardzala LJ, Horton ES. Exercise training increases GLUT‐4 protein in rat adipose cells. Am J Physiol 1993;264(6 Part 1):E882–E889. - PubMed
    1. Lundgren M, Svensson M, Lindmark S, Renström F, Ruge T, Eriksson JW. Fat cell enlargement is an independent marker of insulin resistance and ‘hyperleptinaemia’. Diabetologia 2007;50:625–633. - PubMed
    1. Gollisch KS, Brandauer J, Jessen N, et al. Effects of exercise training on subcutaneous and visceral adipose tissue in normal‐ and high‐fat diet‐fed rats. Am J Physiol Endocrinol Metab 2009;297:E495–E504. - PMC - PubMed

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