Effects of Soy-derived Diets on Plasma and Liver Lipids, Glucose Tolerance, and Longevity in Normal, Long-lived and Short-lived Mice

Abstract

We examined the effects of diets based on a low isoflavone or a high isoflavone soy protein isolates in normal, growth-hormone receptor knockout and Ames dwarf, and Prop 1^df mice that are hypoinsulinemic, insulin-sensitive, and exceptionally long-lived, as well as in growth hormone transgenic mice that are hyperinsulinemic, insulin-resistant, dyslipidemic, and short-lived. Soybean diets tended to normalize plasma cholesterol levels in dwarf and transgenic mice, while low isoflavone diet reduced plasma triglycerides in most of the examined genotypes. The effects of low isoflavone and high isoflavone diets on the levels of free and esterified cholesterol in the liver were strongly genotype-dependent. Fasting blood glucose levels were reduced and glucose tolerance improved by both low isoflavone and high isoflavone diets in growth hormone-transgenic mice and in their normal siblings. Glucose tolerance was also improved by high-isoflavone diet in growth hormone receptor knockout mice. Lifespan was increased by low isoflavone diet in normal mice from two of the examined stocks. High isoflavone diet increased lifespan in normal animals from one line, but reduced lifespan of normal mice from a different line. We conclude that dietary soy protein intake can improve plasma and hepatic lipid profiles, reduce fasting glucose, enhance capacity for glucose tolerance, and prolong life, but all of these effects are strongly genotype-dependent.

Key words

Soy diets · Lipids · Glucose · Isoflavone · GH · Longevity

References

• 1 Adlercreutz H. Epidemiology of phytoestrogens.  Baillieres Clin Endocrinol Metab. 12;  1998 605-623
• 2 Suzuki M, Wilcox B J, Wilcox C D. Implications from and for food cultures for cardiovascular disease: longevity.  Asia Pac J Clin Nutr. 2001;  10 165-171
• 3 Anderson J W, Johnstone B M, Cook-Newell M E. Meta-analysis of the effects of soy protein intake on serum lipids.  N Engl J Med. 1995;  333 276-282
• 4 Anthony M S, Clarkson T B, Williams J K. Effects of soy isoflavones on atherosclerosis: potential mechanisms.  Am J Clin Nutr [Suppl]. 1998;  68 1390S-1393S
• 5 Aoyama T, Fukui K, Takamatsu K, Hashimoto Y, Yamamoto T. Soy protein isolate and its hydrolysate reduce body fat of dietary obese rats and genetically obese mice (yellow KK).  Nutrition. 2000;  16 349-354
• 6 Lavigne C, Marette A, Jacques H. Cod and soy proteins compared with casein improve glucose tolerance and insulin sensitivity in rats.  Am J Physiol. 2000;  278 E491-E500
• 7 Anthony M S, Clarkson T B. et al . Soybean isoflavones improve cardiovascular risk factors without affecting the reproductive system of peripubertal rhesus monkeys.  Journal of Nutrition. 1996;  126 43-50
• 8 Peluso M R, Winters T A, Shanahan M F, Banz W J. A cooperative interaction between soy protein and its isoflavone-enriched fraction lowers hepatic lipids in male obese Zucker rats and reduces blood platelet sensitivity in male Sprague-Dawley rats.  J Nutr. 2000;  130 2333-2342
• 9 Iwasaki , K , Gleiser C A. et al . The influence of dietary protein source on longevity and age-related disease processes of Fischer rats.  Journal of Gerontology. 1988;  43 B5-B12
• 10 Coward L, Barnes N C. et al . Genistein, daidzein, and their β-glycoside conjugates: Antitumor isoflavones in soybean foods from American and Asian diets.  J Agric Food Chem. 1993;  41 1961-1967
• 11 Kurzer M S, Xu X. Dietary phytoestrogens.  Annual Review of Nutrition. 1997;  17 353-381
• 12 Behl C, Skurella T. et al . Neuroprotection against oxidative stress by estrogens: structure-activity relationship.  Molecular Pharmacolgy. 1997;  51 535-541
• 13 Brown-Borg H M, Borg K E. et al . Dwarf mice and the ageing process.  Nature. 1996;  384
• 14 Coshigano K T, Clemmons D, Bellush L L, Kopchick J J. Assessment of growth parameters and lifespan of GHR/BP gene-disrupted mice.  Endocrinology. 2000;  141 2608-2613
• 15 Cecim M, Bartke A. et al . Expression of human, but not bovine growth hormone genes promotes development of mammary tumors in transgenic mice.  Transgenics. 1994;  1 431-437
• 16 Bartke A, Chandrashekar V. et al . Consequences of growth hormone (GH) overexpression and GH resistance.  Neuropeptides. 2002;  36 201-208
• 17 Bartke A, Coschigano K. et al . Genes that prolong life: Relationships of growth hormone and growth to aging and lifespan Journal of Gerontology.  Biological Sciences. 2001;  56A B340-B349
• 18 Davidson M B. Effect of growth hormone on carbohydrate and lipid metabolism.  Endocr Rev. 1987;  8 115-131
• 19 Rosen T, Wilhelmsen L, Bengtsson B-A. Altered lipid pattern explains increased cardiovascular mortality in hypopituitary patients with growth hormone deficiency.  Clin Endocrinol. 1998;  48 525-527
• 20 Rudling M, Parini P, Angelin B. Effects of growth hormone on hepatic cholesterol metabolism. Lessons learned from studies in rats and humans.  Growth Horm IGF Res. 1999;  9 1-7
• 21 Castro G FM, Escobar-Morreale H F, Ortega H. et al . Effects of normalization of GH hypersecretion on lipoprotein(a) and other lipoprotein serum levels in acromegaly.  Clin Endocrinol. 2000;  53 313-319
• 22 Zhou Y, Xu B C, Maheshwari H G. et al . A mammalian model for Laron syndrome produced by targeted disruption of the mouse growth hormone receptor/binding protein gene (the Laron mouse).  Proc Natl Acad Sci USA. 1997;  94 13215-13220
• 23 Bartke A. Delayed aging in Ames dwarf mice. Relationships to endocrine function and body size.  Results Probl Cell Differ. 2000;  29 181-202
• 24 Selden R F, Yun J S. et al . Glucocorticoid regulation of human growth hormone expression in transgenic mice and transiently transfected cells.  Journal of Endocrinology. 1989;  122 49-60
• 25 McGrane M M, deVente J, Yun J. et al . Tissue specific expression and dietary regulation of chimeric phosphoenolpyruvate carboxykinase/bovine growth hormone gene in transgenic mice.  J Biol Chem. 1988;  16 11443-11451
• 26 Reeves P G, Nielsen F H, Fahey, Jr G C. AIN-93 Purified diets for laboratory rodents: final report of the American Institute of Nutrition Ad Hoc Writing Committee on the reformulation of the AIN-76A rodent diet.  J Nutr. 1993;  123 1939-1951
• 27 Folch J, Lees M, Sloane-Stanley G H. A simple method for the isolation and purification of total lipids from animal tissues.  J Biol Chem. 1957;  226 497-509
• 28 Allain C C, Poon L S, Chan C SG, Richmond W, Fu P C. Enzymatic determination of total serum cholesterol.  Clin Chem. 1974;  20 470-475
• 29 Fletcher M J. A colorimetric method for estimating serum triglycerides.  Clin Chim Acta. 1968;  22 393-397
• 30 Bucolo G, David H. Quantitative determination of serum triglycerides by the use of enzymes.  Clin Chem. 1973;  19 476-482
• 31 Cline J M, Hughes C L, Jr. Phytochemicals for the prevention of breast and endometrial cancer.  Cancer Treatment and Research. 1998;  94 107-134
• 32 Ng V L, Coshigano K, Kopchick J J, Bezerra J A, Howles P, Yeh Y Y, Tso P. Abnormal liver lipids in mice with a targeted disruption of the growth hormone receptor/binding protein (GHR/BP) gene.  Gastroenterology. 1999;  116 A630
• 33 Hauck S J, Hunter W S, Danilovich N, Kopchick J J, Bartke A. Reduced levels of thyroid hormones, insulin, and glucose, and lower body core temperature in the growth hormone receptor/binding protein knockout mouse.  Exp Biol Med. 2001;  226 552-558
• 34 Laron Z, Pertzelan A, Karp M. Pituitary dwarfism with high serum levels of growth hormone.  Isr J Med Sci. 1968;  4 883-894
• 35 Johannsson G, Bengtsson B-A. Growth hormone and the metabolic syndrome.  J Endocrinol Invest. 1999;  22 41-46
• 36 Borg K E, Brown-Borg H M, Bartke A. Assessment of the primary adrenal cortical and pancreatic hormone basal levels in relation to plasma glucose and age in the unstressed Ames dwarf mouse.  Proc Soc Exp Biol Med. 1995;  210 126-133
• 37 Brown N M, Setchell K D. Animal models impacted by phytoestrogens in commercial chow: implications for pathways influenced by hormones.  Lab Invest. 2001;  81 735-747
• 38 Valera A, Rodriguez-Gil J E, Yun J S, McGrane M M, Hanson R W, Bosch F. Glucose metabolism in transgenic mice containing a chimeric P-enolpyruvate carboxykinase/bovine growth hormone gene.  FASEB J. 1993;  7 791-800
• 39 Dominici F P, Cifone D, Bartke A, Turyn D. Alterations in the early steps of the insulin-signaling system in skeletal muscle of GH-transgenic mice.  Am J Physiol. 1999;  277 E447-E454
• 40 Foss M C, Paula F JA, Paccola G MGF, Piccinato C E. Peripheral glucose metabolism in human hyperprolactinemia.  Clin Endocrinol. 1995;  43 721-726
• 41 Hartree A S, Kovacic N, Thomas M. Growth-promoting and luteotrophic activities of human growth hormone.  J Endocrinol. 1965;  33 249-258
• 42 Jager W, Winter O, Halper B. et al . Modulation of liver canalicular transport processes by the tyrosine-kinase inhibitor genistein: implications of genistein metabolism in the rat.  Hepatology. 1997;  26 1467-1476
• 43 Sirtori C R, Lovati M R, Manzoni C, Monetti M, Pazzucconi F, Gatti E. Soy and cholesterol reduction: clinical experience.  J Nutr. 1995;  125 598S-605S
• 44 Lovati M R, Allievi L, Sirtori C R. Accelerated early catabolism of very low density lipoproteins in rats after dietary soy proteins.  Atherosclerosis. 1985;  56 243-246
• 45 Iritani N, Hosomi H, Fukuda H, Tada K, Ikeda H. Soybean protein suppresses hepatic lipogenic enzyme gene expression in Wistar fatty rats.  J Nutr. 1996;  126 380-388
• 46 Rudling M, Norstedt G, Olivecrona H, Reihner E, Gustafsson J-A, Angelin B. Importance of growth hormone for the induction of hepatic low density lipoprotein receptors.  Proc Natl Acad Sci USA. 1992;  89 6983-6987
• 47 Christ E R, Wierzbicki A S, Cummings M H, Umpleby A M, Russell-Jones D L. Dynamics of lipoprotein metabolism in adult growth hormone deficiency.  J Endocrinol Invest. 1999;  22 16-21
• 48 Bornstein J, Ng F M, Heng D, Wong K P. Metabolic actions of pituitary growth hormone. I. Inhibition of acetyl CoA carboxylase by human growth hormone and a carboxyl terminal part sequence acting through a second messenger.  Acta Endocrinol. 1983;  103 479-486
• 49 Kuppusamy U R, Das N P. Effects of flavonoids on cyclic AMP phosphodiesterase and lipid mobilization in rat adipocytes.  Biochem Pharmacol. 1992;  44 1307-1315
• 50 Randle P J, Priestman D A, Mistry S C, Halsall A. Glucose fatty acid interactions and the regulation of glucose disposal.  J Cell Biochem. 1994;  55S 1-11
• 51 Mezei O, Banz W J, Steger R W, Peluso M R, Winters T A, Shay N. Soy Isoflavones Exert Antidiabetic and Hypolipidemic Effects through the PPAR Pathways in Obese Zucker Rats and Murine RAW 264.7 Cells.  J Nutr. 2003;  133 238-1243
• 52 Paolisso G, Ferrannini E, Sgambato S, Varricchio M, D’Onofrio F. Hyperinsulinemia in patients with hypercholesterolemia.  J Clin Endocrinol Metab. 1992;  75 1409-1412
• 53 Sheu W H-H, Shieh S-M, Fuh M M-T, Shen D D-C, Jeng C-Y, Chen Y-D I, Reaven G M. Insulin resistance, glucose intolerance, and hyperinsulinemia. Hypertriglyceridemia versus hypercholesterolemia.  Arterioscler Thromb. 1993;  13 367-370
• 54 Wolf E, Kahnt E. et al . Effects of long-term elevated serum levels of growth hormone on life expectancy of mice: Lessons from transgenic animal models.  Mechanisms of Ageing and Development. 1993;  68 71-87