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Fatty acid desaturase regulation in adipose tissue by dietary composition is independent of weight loss and is correlated with the plasma triacylglycerol response^1,2,3

¹ From the Children's Hospital Oakland Research Institute, Oakland, CA (LMM and RMK); the Center for Excellence in Nutritional Genomics, University of California, Davis, CA (LMM, KD, JPG, and RMK); and the Department of Pathology and Laboratory Medicine, School of Medicine, University of California, Davis, CA (RRD and JPG)

Background:Atherogenic dyslipidemia associated with elevated plasma triacylglycerol concentrations and reduced HDL is improved by both caloric restriction and reduced carbohydrate consumption.

Objective:We aimed to identify the molecular pathways responsive to both caloric restriction and dietary composition within adipose tissue by monitoring transcriptional expression.

Design:Subcutaneous adipose tissue biopsy specimens were obtained from 131 moderately overweight men [body mass index (in kg/m²): 29.2 ± 2.0] after 1 wk of a basal diet [54%, 16%, and 30% carbohydrate, protein, and fat, respectively; 7% saturated fat), after 3 wk with 1 of 4 randomized diets [basal diet; moderate-carbohydrate (39%) diet; low-carbohydrate (26%) and low-saturated-fat (9%) diet; low-carbohydrate (26%) and high-saturated-fat (15%) diet], after 5 wk of acute weight loss with a randomized diet (–1103.0 ± 216.5 kcal/d, which resulted in a loss of 10.0 ± 3.3 lb, or 4.5 ± 1.5 kg), and after 4 wk of being stabilized at a reduced weight. Transcriptional response was identified by using expression array analysis and was confirmed by using real-time polymerase chain reaction analysis.

Results:Of the 1473 transcripts significantly decreased in expression in response to acute weight loss, 30 were responsive to isocaloric alterations in dietary composition, including stearoyl-coenzyme A desaturase (SCD), fatty acid desaturases 1 and 2 (FADS1 and FADS2), and diacylglycerol transferase 2 (DGAT2). Response was confirmed by real-time polymerase chain reaction analysis for these genes (P < 0.003). SCD expression in response to isocaloric dietary change was most strongly correlated with carbohydrate intake (P = 0.019) and, with the low-carbohydrate diet, SCD expression was inversely correlated with saturated fat intake (P = 0.05). Triacylglycerol responses to changes in dietary composition were independently correlated with SCD (P = 0.003) and DGAT2 (P = 0.05) responses.

Conclusions:SCD expression in adipose tissue is independently regulated by weight loss and by carbohydrate and saturated fat intakes. Moreover, SCD and DGAT2 expression may be involved in dietary regulation of systemic triacylglycerol metabolism.

Key Words: Gene expression • gene expression microarray • gene transcription • adipose tissue • weight loss • dietary carbohydrate • dietary saturated fat • fatty acid desaturases • triacylglycerol

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