Free fatty acids, lipopolysaccharide and IL-1α induce adipocyte manganese superoxide dismutase which is increased in visceral adipose tissues of obese rodents.
Excess fat storage in adipocytes is associated with increased generation of reactive oxygen species (ROS) and impaired activity of antioxidant mechanisms. Manganese superoxide dismutase (MnSOD) is a mitochondrial enzyme involved in detoxification of ROS, and objective of the current study is to analyze expression and regulation of MnSOD in obesity. MnSOD is increased in visceral but not subcutaneous fat depots of rodents kept on high fat diets (HFD) and ob/ob mice. MnSOD is elevated in visceral adipocytes of fat fed mice and exposure of differentiating 3T3-L1 cells to lipopolysaccharide, IL-1α, saturated, monounsaturated and polyunsaturated free fatty acids (FFA) upregulates its level. FFA do not alter cytochrome oxidase 4 arguing against overall induction of mitochondrial enzymes. Upregulation of MnSOD in fat loaded cells is not mediated by IL-6, TNF or sterol regulatory element binding protein 2 which are induced in these cells. MnSOD is similarly abundant in perirenal fat of Zucker diabetic rats and non-diabetic animals with similar body weight and glucose has no effect on MnSOD in 3T3-L1 cells. To evaluate whether MnSOD affects adipocyte fat storage, MnSOD was knocked-down in adipocytes for the last three days of differentiation and in mature adipocytes. Knock-down of MnSOD does neither alter lipid storage nor viability of these cells. Heme oxygenase-1 which is induced upon oxidative stress is not altered while antioxidative capacity of the cells is modestly reduced. Current data show that inflammation and excess triglyceride storage raise adipocyte MnSOD which is induced in epididymal adipocytes in obesity.
Department of Internal Medicine I, Regensburg University Hospital, Regensburg, Germany.
Sabrina
S
Krautbauer
Department of Internal Medicine I, Regensburg University Hospital, Regensburg, Germany.
Kristina
K
Eisinger
Department of Internal Medicine I, Regensburg University Hospital, Regensburg, Germany.
Markus
M
Neumeier
Department of Internal Medicine I, Regensburg University Hospital, Regensburg, Germany.
Yvonne
Y
Hader
Department of Internal Medicine I, Regensburg University Hospital, Regensburg, Germany.
Roland
R
Buettner
Department of Internal Medicine II, Regensburg University Hospital, Regensburg, Germany.
Peter M
PM
Schmid
Institute of Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany.
Charalampos
C
Aslanidis
Department of Internal Medicine I, Regensburg University Hospital, Regensburg, Germany.
Christa
C
Buechler
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D059305:Diet, High-Fat; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation; D053582:Interleukin-1alpha / Q000494:pharmacology*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D050152:Intra-Abdominal Fat / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009765:Obesity / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D015398:Signal Transduction; D051782:Sterol Regulatory Element Binding Protein 2 / Q000235:genetics / Q000378:metabolism; D050151:Subcutaneous Fat / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D005230:Fatty Acids, Nonesterified; D053582:Interleukin-1alpha; D015850:Interleukin-6; D008070:Lipopolysaccharides; D034741:RNA, Small Interfering; D051782:Sterol Regulatory Element Binding Protein 2; D014409:Tumor Necrosis Factor-alpha; D013482:Superoxide Dismutase