Abstract
Interleukin (IL)‐6 is released from skeletal muscle (SkM) during exercise and has been shown to affect hepatic metabolism. It is, however, unknown whether SkM IL‐6 is involved in the regulation of exercise training‐induced counteraction of changes in carbohydrate and lipid metabolism in the liver in response to high‐fat diet (HFD) feeding. Male SkM‐specific IL‐6 KO (MKO) and Floxed mice were subjected to Chow diet, HFD or HFD combined with exercise training (HFD ExTr) for 16 weeks. Hepatic phosphoenolpyruvate carboxykinase (PEPCK) protein content decreased with both HFD and HFD ExTr in Floxed mice, but increased in IL‐6 MKO mice on HFD. In addition, the intrahepatic glucose concentration was in IL‐6 MKO mice higher in HFD than chow. Within HFD ExTr mice, hepatic glucose‐6‐phosphatase (G6Pase) 36 kDa protein content was higher in IL‐6 MKO than Floxed mice. Hepatic pyruvate dehydrogenase kinase (PDK) 4 and PDK2 protein content was in Floxed mice lower in HFD ExTr than Chow. In addition, hepatic ACC1‐phosphorylation was higher and ACC1 protein lower in HFD. Together this suggests that SkM IL‐6 regulates hepatic glucose metabolism, but does not seem to be of major importance for the regulation of oxidative capacity or lipogenesis in liver during HFD or HFD combined with exercise training.
Highlights
It has been shown that hepatic triglyceride (TG) content is increased when rodents are fed a high-fat diet (HFD) (Rector et al 2008; Gollisch et al 2009) and is higher in obese than lean human subjects (Fabbrini et al 2010)
While hepatic glucose concentration was ~30% higher (P < 0.05) in HFD and HFD ExTr than Chow within IL-6 Male SkM-specific IL-6 KO (MKO) mice (Fig. 1A), the lactate concentration did not change with HFD or HFD combined with exercise training in either genotype (Fig. 1B)
The main finding of this study is that skeletal muscle (SkM) IL-6 seems to contribute to the regulation of markers of gluconeogenesis in response to HFD, without playing a major role in the regulation of hepatic fat metabolism or oxidative capacity in mice on HFD or HFD combined with exercise training
Summary
It has been shown that hepatic triglyceride (TG) content is increased when rodents are fed a high-fat diet (HFD) (Rector et al 2008; Gollisch et al 2009) and is higher in obese than lean human subjects (Fabbrini et al 2010) Such accumulation of intracellular lipids has been suggested to induce hepatic insulin resistance and reduce hepatic oxidative capacity (Gollisch et al 2009), potentially leading to metabolically related diseases.
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