Dietary Lipid-dependent Regulation of De Novo Lipogenesis and Lipid Partitioning by Ketogenic Essential Amino Acids in Mice

Overview

Journal Nutr Diabetes

Specialties Endocrinology
Nutritional Sciences

Date 2012 Nov 17

PMID 23154504

Citations 6

Authors

N Nishikata

N Shikata

Y Kimura

Y Noguchi

Affiliations

Soon will be listed here.

Abstract

Background: We have previously reported that dietary ketogenic amino acids (KAAs) modulate hepatic de novo lipogenesis (DNL) and prevent hepatic steatosis in mice. However, the dependence of the metabolic phenotypes generated by KAA on the type of dietary lipid source remains unclear.

Objective: The aim of this study was to assess the effect of KAA combined with different dietary lipid sources on hepatic DNL and tissue lipid partitioning in mice.

Design: We compared three different KAA-supplemented diets, in which a portion of the dietary protein was replaced by five major essential amino acids (Leu, Ile, Val, Lys and Thr) in high-fat diets based on palm oil (PO), high-oleic safflower oil (FO) or soy oil (SO). To compare the effects of these diets in C57B6 mice, the differential regulation of DNL and dietary lipid partitioning due to KAA was assessed using stable isotopic flux analysis.

Results: The different dietary oils showed strikingly different patterns of lipid partitioning and accumulation in tissues. High-PO diets increased both hepatic and adipose triglycerides (TG), whereas high-FO and high-SO diets increased hepatic and adipose TG, respectively. Stable isotopic flux analysis revealed high rates of hepatic DNL in high-PO and high-FO diets, whereas it was reduced in the high-SO diet. KAA supplementation in high-PO and high-FO diets reduced hepatic TG by reducing the DNL of palmitate and the accumulation of dietary oleate. However, KAA supplementation in the high-SO diet failed to reduce hepatic DNL and TG. Interestingly, KAA reduced SO-induced accumulation of hepatic linoleate and enhanced SO-induced accumulation of dietary oleate.

Conclusions: Overall, the reduction of hepatic TG by KAA is dependent on dietary lipid sources and occurs through the modulation of DNL and altered partitioning of dietary lipids. The current results provide further insight into the underlying mechanisms of hepatic lipid reduction by amino acids.

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References

Piers L, Walker K, Stoney R, Soares M, ODea K . The influence of the type of dietary fat on postprandial fat oxidation rates: monounsaturated (olive oil) vs saturated fat (cream). Int J Obes Relat Metab Disord. 2002; 26(6):814-21. DOI: 10.1038/sj.ijo.0801993. View

Merkel M, Hudgins L, Breslow J . Compared with saturated fatty acids, dietary monounsaturated fatty acids and carbohydrates increase atherosclerosis and VLDL cholesterol levels in LDL receptor-deficient, but not apolipoprotein E-deficient, mice. Proc Natl Acad Sci U S A. 2001; 98(23):13294-9. PMC: 60864. DOI: 10.1073/pnas.231490498. View

Suresh Y, Das U . Differential effect of saturated, monounsaturated, and polyunsaturated fatty acids on alloxan-induced diabetes mellitus. Prostaglandins Leukot Essent Fatty Acids. 2006; 74(3):199-213. DOI: 10.1016/j.plefa.2005.11.006. View

Zhu F, Liu S, Chen X, Huang Z, Zhang D . Effects of n-3 polyunsaturated fatty acids from seal oils on nonalcoholic fatty liver disease associated with hyperlipidemia. World J Gastroenterol. 2008; 14(41):6395-400. PMC: 2766124. DOI: 10.3748/wjg.14.6395. View

Hill J, Peters J, Lin D, Yakubu F, Greene H, Swift L . Lipid accumulation and body fat distribution is influenced by type of dietary fat fed to rats. Int J Obes Relat Metab Disord. 1993; 17(4):223-36. View

Kim S, Kim H, Kim T, Im S, Park S, Lee I . SREBP-1c mediates the insulin-dependent hepatic glucokinase expression. J Biol Chem. 2004; 279(29):30823-9. DOI: 10.1074/jbc.M313223200. View

Styczynski M, Moxley J, Tong L, Walther J, Jensen K, Stephanopoulos G . Systematic identification of conserved metabolites in GC/MS data for metabolomics and biomarker discovery. Anal Chem. 2007; 79(3):966-73. DOI: 10.1021/ac0614846. View

Abete I, Astrup A, Martinez J, Thorsdottir I, Zulet M . Obesity and the metabolic syndrome: role of different dietary macronutrient distribution patterns and specific nutritional components on weight loss and maintenance. Nutr Rev. 2010; 68(4):214-31. DOI: 10.1111/j.1753-4887.2010.00280.x. View

Chu S, Samonds K, Seronde Jr J, HEGSTED D . Protein utilization and lysine metabolism in obese and non-obese growing rats. J Nutr. 1978; 108(4):567-77. DOI: 10.1093/jn/108.4.567. View

10.

Oosterveer M, van Dijk T, Tietge U, Boer T, Havinga R, Stellaard F . High fat feeding induces hepatic fatty acid elongation in mice. PLoS One. 2009; 4(6):e6066. PMC: 2699051. DOI: 10.1371/journal.pone.0006066. View

11.

Chen Q, Reimer R . Dairy protein and leucine alter GLP-1 release and mRNA of genes involved in intestinal lipid metabolism in vitro. Nutrition. 2008; 25(3):340-9. PMC: 3827015. DOI: 10.1016/j.nut.2008.08.012. View

12.

Noguchi Y, Zhang Q, Sugimoto T, Furuhata Y, Sakai R, Mori M . Network analysis of plasma and tissue amino acids and the generation of an amino index for potential diagnostic use. Am J Clin Nutr. 2006; 83(2):513S-519S. DOI: 10.1093/ajcn/83.2.513S. View

13.

She P, Reid T, Bronson S, Vary T, Hajnal A, Lynch C . Disruption of BCATm in mice leads to increased energy expenditure associated with the activation of a futile protein turnover cycle. Cell Metab. 2007; 6(3):181-94. PMC: 2693888. DOI: 10.1016/j.cmet.2007.08.003. View

14.

Laviano A, Meguid M, Inui A, Rossi-Fanelli F . Role of leucine in regulating food intake. Science. 2006; 313(5791):1236-8. DOI: 10.1126/science.313.5791.1236b. View

15.

Doucet E, Almeras N, White M, Despres J, Bouchard C, Tremblay A . Dietary fat composition and human adiposity. Eur J Clin Nutr. 1998; 52(1):2-6. DOI: 10.1038/sj.ejcn.1600500. View

16.

Lavau M, Hashim S . Effect of medium chain triglyceride on lipogenesis and body fat in the rat. J Nutr. 1978; 108(4):613-20. DOI: 10.1093/jn/108.4.613. View

17.

Worgall T, Sturley S, Seo T, Osborne T, Deckelbaum R . Polyunsaturated fatty acids decrease expression of promoters with sterol regulatory elements by decreasing levels of mature sterol regulatory element-binding protein. J Biol Chem. 1998; 273(40):25537-40. DOI: 10.1074/jbc.273.40.25537. View

18.

St-Onge M, Jones P . Greater rise in fat oxidation with medium-chain triglyceride consumption relative to long-chain triglyceride is associated with lower initial body weight and greater loss of subcutaneous adipose tissue. Int J Obes Relat Metab Disord. 2003; 27(12):1565-71. DOI: 10.1038/sj.ijo.0802467. View

19.

Fabbrini E, Sullivan S, Klein S . Obesity and nonalcoholic fatty liver disease: biochemical, metabolic, and clinical implications. Hepatology. 2009; 51(2):679-89. PMC: 3575093. DOI: 10.1002/hep.23280. View

20.

Viviani R, SECHI A, Lenaz G . Lipid metabolism in fatty liver of lysine- and threonine-deficient rats. J Lipid Res. 1966; 7(4):473-8. View