High-Fat Diet Induces Distinct Metabolic Response in Interleukin-6 and Tumor Necrosis Factor-α Knockout Mice.
Studies suggest interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) may be beneficial in obesity-related disorders with inconsistent results. This study was designed to investigate and compare their pathophysiological roles in lipid metabolism with gene knockout approach. Male wild-type (WT), IL-6 knockout (IL-6-/-), and TNF-α knockout (TNF-α-/-) mice were maintained on either a chow diet or a high-fat diet (HFD) for 12 weeks. Indices of lipid metabolism in blood, adipose, and liver were determined. Our data showed that IL-6-/-and TNF-α-/-mice were more pronounced in body weight gains, hypercholesterolemia, fasting and post-load hyperglycemia on a chow diet or a HFD compared with WT mice. In WT mice feeding on a HFD, lipolysis and glyceroneogenesis were enhanced, lipogenesis was inhibited in adipose tissue; lipogenesis was increased in liver tissue. IL-6-/-mice on a chow diet or a HFD showed similar metabolic phenotypes as WT mice on a HFD, since those mice had similar expression profiles of lipid-related genes in adipose tissue and liver. However, TNF-α-/-mice were different. Therefore, IL-6-/-and TNF-α-/-mice showed different hepatic triglyceride infiltration in response to different diets. Our study suggests that complete blockage of IL-6 and TNF-α is unbeneficial in obesity and obesity-related metabolic disorders in mice.
1 Laboratory of Endocrinology and Metabolism, Department of Endocrinology, West China Hospital, Sichuan University , Chengdu, China .
Xiang
X
Chen
2 Department of Orthopedics, West China Hospital, Sichuan University , Chengdu, China .
Quan
Q
Gong
1 Laboratory of Endocrinology and Metabolism, Department of Endocrinology, West China Hospital, Sichuan University , Chengdu, China .
Chun-Yu
CY
Wang
1 Laboratory of Endocrinology and Metabolism, Department of Endocrinology, West China Hospital, Sichuan University , Chengdu, China .
Kun
K
Zhang
1 Laboratory of Endocrinology and Metabolism, Department of Endocrinology, West China Hospital, Sichuan University , Chengdu, China .
Xiao
X
Ji
1 Laboratory of Endocrinology and Metabolism, Department of Endocrinology, West China Hospital, Sichuan University , Chengdu, China .
Ya-Xi
YX
Chen
1 Laboratory of Endocrinology and Metabolism, Department of Endocrinology, West China Hospital, Sichuan University , Chengdu, China .
Xi-Jie
XJ
Yu
D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects*; D015850:Interleukin-6 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha
inflammation; interleukin-6; lipid metabolism; obesity; tumor necrosis factor-α