Skip to main content
ARS Home » Pacific West Area » Davis, California » Western Human Nutrition Research Center » Obesity and Metabolism Research » Research » Publications at this Location » Publication #319517
Title: Zinc transporter 7 deficiency affects lipid synthesis in adipocytes by inhibiting insulin-dependent Akt activity and glucose uptake

Author
item TEPAAMORNDECH, SURAPUN - University Of California
item Kirschke, Catherine
item Pedersen, Theresa
item Keyes, William
item Newman, John
item Huang, Liping

Submitted to: FEBS Journal
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/28/2015
Publication Date: 11/1/2015
Citation: Tepaamorndech, S., Kirschke, C.P., Pedersen, T.L., Keyes, W.R., Newman, J.W., Huang, L. 2015. Zinc transporter 7 deficiency affects lipid synthesis in adipocytes by inhibiting insulin-dependent Akt activity and glucose uptake. FEBS Journal. 283(2):378-394. doi: 10.1111/febs.13582.

Interpretive Summary: Mice without the presence of a zinc carrier (ZnT7) in the body due to a null-mutation 7 are mildly zinc deficient, accompanied with low body weight gain and body fat accumulation. To investigate the underlying mechanism of Znt7 deficiency in body fat deposition, we investigated fatty acid composition and insulin sensitivity in visceral (epididymal) and subcutaneous fat pads from Znt7 deficient and control mice. We showed that Znt7 deficiency had differentially adverse effects on fatty acid metabolism and insulin action in subcutaneous fat but not epididymal fat in mice, consistent with the ZnT7 protein expression pattern in fat tissues. Importantly, we found that the expression of ZnT7 protein was induced by lipogenic differentiation (fat cell development) and reached a peak when the adipocyte (fat cell) was fully differentiated in mouse 3T3-L1 adipocytes. We demonstrated, using Znt7 knockdown adipocytes (Znt7KD, the Znt7 expression was reduced to 30 % of the normal level), that reduction in Znt7 expression blunted the activities of the signaling 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 fat cell differentiation was not affected by Znt7KD in 3T3-L1 adipocytes. These findings strongly suggest a role for ZnT7 in the process of fat formation in adipocytes.

Technical Abstract: Mice deficient for zinc transporter 7 (Znt7) are mildly zinc deficient, accompanied with low body weight gain and body fat accumulation. To investigate the underlying mechanism of Znt7 deficiency in body adiposity, we investigated 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 differentially adverse effects on fatty acid metabolism and insulin action in subcutaneous fat but not 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 the activities 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 preadipocyte differentiation, including Ppar' and C/Ebp', appeared not to be affected by Znt7KD in 3T3-L1 adipocytes. These findings strongly suggest a role for ZnT7 in adipocyte lipogenesis.