title: Zinc transporter 7 deficiency affects lipid synthesis in adipocytes by inhibiting insulin-dependent Akt activation and glucose uptake.
abstract: Mice deficient for zinc transporter 7 protein (ZnT7) are mildly zinc deficient with low body weight gain and body fat accumulation. To investigate the underlying mechanism of ZnT7 deficiency in body adiposity, we examined fatty acid composition and insulin sensitivity in visceral (epididymal) and subcutaneous fat pads from Znt7 knockout and control mice. We showed that ZnT7 deficiency had adverse effects on fatty acid metabolism and insulin action in subcutaneous fat but not in epididymal fat in mice, consistent with the ZnT7 protein expression pattern in adipose tissues. Importantly, we found that the expression of ZnT7 protein was induced by lipogenic differentiation and reached a peak when the adipocyte was fully differentiated in mouse 3T3-L1 adipocytes. We demonstrated, using Znt7 knockdown (Znt7KD) 3T3-L1 adipocytes, that reduction in Znt7 expression blunted activations of the signal transduction pathways that regulated both basal and insulin-stimulated glucose uptake in adipocytes, resulting in low glucose uptake and lipid accumulation. The expression of the signaling mediators critical for the initiation of pre-adipocyte differentiation, including Pparγ and C/Ebpα, appeared not to be affected by Znt7KD in 3T3-L1 adipocytes. These findings strongly suggest a role for ZnT7 in adipocyte lipogenesis.
authors.affiliation: Integrative Genetics and Genomics Graduate Group, University of California Davis, CA, USA.
authors.forename: Surapun
authors.initials: S
authors.lastname: Tepaamorndech
authors.affiliation: Obesity and Metabolism Research Unit, USDA/ARS/Western Human Nutrition Research Center, Davis, CA, USA.
authors.forename: Catherine P
authors.initials: CP
authors.lastname: Kirschke
authors.affiliation: Obesity and Metabolism Research Unit, USDA/ARS/Western Human Nutrition Research Center, Davis, CA, USA.
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Pedersen
authors.affiliation: Obesity and Metabolism Research Unit, USDA/ARS/Western Human Nutrition Research Center, Davis, CA, USA.
authors.forename: William R
authors.initials: WR
authors.lastname: Keyes
authors.affiliation: Obesity and Metabolism Research Unit, USDA/ARS/Western Human Nutrition Research Center, Davis, CA, USA.|Department of Nutrition, University of California Davis, CA, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Newman
authors.affiliation: Integrative Genetics and Genomics Graduate Group, University of California Davis, CA, USA.|Obesity and Metabolism Research Unit, USDA/ARS/Western Human Nutrition Research Center, Davis, CA, USA.|Department of Nutrition, University of California Davis, CA, USA.
authors.forename: Liping
authors.initials: L
authors.lastname: Huang
mesh_terms: D041721:3T3-L1 Cells / Q000187:drug effects / Q000378:metabolism; D017667:Adipocytes / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000235:genetics; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D004822:Epididymis / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D008055:Lipids / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D050151:Subcutaneous Fat / Q000378:metabolism
chemical_list: D027682:Cation Transport Proteins; D005227:Fatty Acids; D007328:Insulin; D008055:Lipids; C472293:ZnT7 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose
keywords: 3T3-L1; ZnT7; adipocytes; lipogenesis; zinc homeostasis