English

2011年10月17日

Department of Clinical Nutrition

 

As the only nutritional program attached to a medical school in Japan, the mainstream research has been focused on medical nutrition in our department. In addition to the curriculum of registered dietitian course for undergraduate students, special programs for educational purposes are provided. As a part of the stress and nutrition educational program, a new graduate school lecture/seminar series “stress, mind and nutrition” targeted towards graduate students/young researchers are set up. As for educational program of functional food development and nutritional care in clinical nutrition, world-renowned researchers both from Japanese research institutions and from abroad were invited.
Furthermore, nutritional care in Nutrition Support Team (NST) of University hospital made all patients improved QOL. The research theme are (1) the role of phosphate in bone and kidney diseases, (2) functional food development for metabolic and stress control, (3) endothelial function and atherosclerosis, (4) nutritional care of hepatic cirrhosis and transplantation and others. These research and educational programs were achieved by the collaboration with 4 staffs, 20 postgraduate and 9 undergraduate students. We are very glad to accept you as undergraduate student or postgraduate student for your bright future.

Research Activities

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1) Nutritional science on metabolic and stress control

Pronounced changes in the human environment, and in human behavior and lifestyle, have accompanied globalization and have resulted in escalating rates of lifestyle related diseases such as obesity, type 2 diabetes, osteoporosis and others. Psychological stress is associated with increased oxidant production and oxidative damage, and thus long-term exposure to psychological stressors may enhance the risk of many diseases.
The oxidative stress associated with psychological and/or emotional stress might be an appropriate target for assessing the preventive potentiality of food supplements. Early insulin secretion in response to an oral glucose load is important to control glucose metabolism. Impairment of this response is the cause of postprandial hyperglycemia which induces insulin resistance. Hyperglycemia enhances production of reactive oxygen species (ROS). Therefore, development of functional foods which suppress postprandial glucose level is an important way to prevent cardio-vascular disease and psychological stress.

Recent publication:
Arai H, et al: Effects of a palatinose-based liquid diet (Inslow) on glycemic control and the second meal effect in healthy men. Metabolism 56: 115-121, 2007
Takeda E, et al: Gene expression in low glycemic index diet-impact on metabolic control. Forum of Nutrition, 60:127-139, 2007

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2) Role of foods and nutrients combination

According to the survey of life span, Japanese has the longest life span in the world. It is conceivable that Japanese diet may contribute to this longevity of Japanese. Rice is very important staple food for Japanese, but it has high glycemic index. The effect of food combination with rice based meal on glycemic index was investigated. Typical Japanese food, combination of rice with barley and viscous food, natto, yams, okuras, effectively suppressed glycemic responses to rice based meal and prevent metabolic syndrome.
In animal studies on combination effect of carbohydrate and fatty acids, palatinose feeding (PO and PL) led to significant reductions in visceral fat mass, adipocyte cell size, hyperglycemia, and hyperlipidemia compared with sucrose feeding (SO and SL); pancreatic islet hypertrophy was also prevented by palatinose feeding. Linoleic-acid-fed rats (PL and SL) exhibited reduced insulin-immunoreactive staining of the pancreatic islets, enhanced macrophage infiltration in adipose tissue, and an elevated plasma tumor necrosis factor-a concentration when compared with oleic-acid-fed rats (PO and SO). In conclusion, food combination supported by scientific evidences is important to prevent life style related diseases.

Recent publication:
Sato K, et al: A combination of dietary palatinose and oleic acid ameliorates disorders of glucose and lipid metabolism in Zucker Fatty rats. J Nutr, 137: 1908-1915, 2007

 

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3) Regulation of sub-cellular localization of sodium-dependent phosphate transporter to maintain the phosphate homeostasis

Phosphate homeostasis is mainly regulated by controlling renal phosphate reabsorption activity. Type IIa sodium-dependent phosphate transporter (NaPi-IIa) plays a critical role in the renal phosphate reabsorption. Most of phosphate regulating factors regulate the NaPi-IIa activity transcriptionally and/or translocationally. Recently, it has been clarified that NaPi-IIa forms a macromolecular complex with cytoskeletal proteins, adaptor proteins, and signal transduction proteins on plasma membrane. We have attempted to clarify the molecular components of the NaPi-IIa complex and their functions.

Recent publication:
Nashiki K, et al: Role of membrane microdomains in PTH-mediated down-regulation of NaPi-IIa in opossum kidney cells. Kidney Int. 68:1137-1147, 2005
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1) Nutritional science on metabolic and stress control

Pronounced changes in the human environment, and in human behavior and lifestyle, have accompanied globalization and have resulted in escalating rates of lifestyle related diseases such as obesity, type 2 diabetes, osteoporosis and others. Psychological stress is associated with increased oxidant production and oxidative damage, and thus long-term exposure to psychological stressors may enhance the risk of many diseases.
The oxidative stress associated with psychological and/or emotional stress might be an appropriate target for assessing the preventive potentiality of food supplements. Early insulin secretion in response to an oral glucose load is important to control glucose metabolism. Impairment of this response is the cause of postprandial hyperglycemia which induces insulin resistance. Hyperglycemia enhances production of reactive oxygen species (ROS). Therefore, development of functional foods which suppress postprandial glucose level is an important way to prevent cardio-vascular disease and psychological stress.

Recent publication:
Arai H, et al: Effects of a palatinose-based liquid diet (Inslow) on glycemic control and the second meal effect in healthy men. Metabolism 56: 115-121, 2007
Takeda E, et al: Gene expression in low glycemic index diet-impact on metabolic control. Forum of Nutrition, 60:127-139, 2007

Sakuma M, et al. Dose-dependent effects of barley cooked with white rice on postprandial glucose and desacyl ghrelin levels. J Clin Biochem Nutr. 2009 Mar;44(2):151-9.

Uebanso T, et al. Hypocaloric high-protein diet improves fatty liver and hypertriglyceridemia in sucrose-fed obese rats via two pathways. Am J Physiol Endocrinol Metab. 2009 Jul;297(1):E76-84.

Sakuma M, et al. Improvement of glucose metabolism in patients with impaired glucose tolerance or diabetes by long-term administration of a palatinose-based liquid formula as a part of breakfast.J Clin Biochem Nutr. 2009 Sep;45(2):155-62.

Uebanso T, et al. Paradoxical regulation of human FGF21 by both fasting and feeding signals: is FGF21 a nutritional adaptation factor? PLoS One. 2011;6(8):e22976

Uebanso T, et al. Liver X receptor negatively regulates fibroblast growth factor 21 in the fatty liver induced by cholesterol-enriched diet. J Nutr Biochem. 2012 Jul;23(7):785-90

Nakahashi O, et al. Short-term dietary phosphate restriction up-regulates ileal fibroblast growth factor 15 gene expression in mice. J Clin Biochem Nutr. 2014 Mar;54(2):102-8.



2) Role of foods and nutrients combination

According to the survey of life span, Japanese has the longest life span in the world. It is conceivable that Japanese diet may contribute to this longevity of Japanese. Rice is very important staple food for Japanese, but it has high glycemic index. The effect of food combination with rice based meal on glycemic index was investigated. Typical Japanese food, combination of rice with barley and viscous food, natto, yams, okuras, effectively suppressed glycemic responses to rice based meal and prevent metabolic syndrome.
In animal studies on combination effect of carbohydrate and fatty acids, palatinose feeding (PO and PL) led to significant reductions in visceral fat mass, adipocyte cell size, hyperglycemia, and hyperlipidemia compared with sucrose feeding (SO and SL); pancreatic islet hypertrophy was also prevented by palatinose feeding. Linoleic-acid-fed rats (PL and SL) exhibited reduced insulin-immunoreactive staining of the pancreatic islets, enhanced macrophage infiltration in adipose tissue, and an elevated plasma tumor necrosis factor-a concentration when compared with oleic-acid-fed rats (PO and SO). In conclusion, food combination supported by scientific evidences is important to prevent life style related diseases.

Recent publication:
Sato K, et al: A combination of dietary palatinose and oleic acid ameliorates disorders of glucose and lipid metabolism in Zucker Fatty rats. J Nutr, 137: 1908-1915, 2007

Taniguchi A, et al. Natto and viscous vegetables in a Japanese style meal suppress postprandial glucose and insulin responses. Asia Pac J Clin Nutr. 2008;17(4):663-8.

Amo K, et al. Effects of xylitol on metabolic parameters and visceral fat accumulation. J Clin Biochem Nutr. 2011 Jul;49(1):1-7

Taiguchi-Fukatsu A, et al. Natto and viscous vegetables in a Japanese-style breakfast improved insulin sensitivity, lipid metabolism and oxidative stress in overweight subjects with impaired glucose tolerance.Br J Nutr. 2012 Apr;107(8):1184-91

Kawakami Y, et al. Gene expression profiling in peripheral white blood cells in response to the intake of food with different glycemic index using a DNA microarray. J Nutrigenet Nutrigenomics. 2013;6(3):154-68

Wanjihia VW, et al. Induction of the hepatic stearoyl-CoA desaturase 1 gene in offspring after isocaloric administration of high fat sucrose diet during gestation.J Clin Biochem Nutr. 2013 Nov;53(3):150-7

Ohminami H, et al. Dietary combination of sucrose and linoleic acid causes skeletal muscle metabolic abnormalities in Zucker fatty rats through specific modification of fatty acid composition. J Clin Biochem Nutr. 2014 Jul;55(1):15-25.



3) Regulation of sub-cellular localization of sodium-dependent phosphate transporter to maintain the phosphate homeostasis

Phosphate homeostasis is mainly regulated by controlling renal phosphate reabsorption activity. Type IIa sodium-dependent phosphate transporter (NaPi-IIa) plays a critical role in the renal phosphate reabsorption. Most of phosphate regulating factors regulate the NaPi-IIa activity transcriptionally and/or translocationally. Recently, it has been clarified that NaPi-IIa forms a macromolecular complex with cytoskeletal proteins, adaptor proteins, and signal transduction proteins on plasma membrane. We have attempted to clarify the molecular components of the NaPi-IIa complex and their functions.

Recent publication:
Nashiki K, et al: Role of membrane microdomains in PTH-mediated down-regulation of NaPi-IIa in opossum kidney cells. Kidney Int. 68:1137-1147, 2005

Tanimura A, et al. Analysis of different complexes of type IIa sodium-dependent phosphate transporter in rat renal cortex using blue-native polyacrylamide gel electrophoresis.J Med Invest. 2011 Feb;58(1-2):140-7.

Yamada F, et al. Role of serine 249 of ezrin in the regulation of sodium-dependent phosphate transporter NaPi-IIa activity in renal proximal tubular cells. J Med Invest. 2013;60(1-2):27-34.





4) Effect of hyperphosphatemia on the vascular function and life-style related diseases

Hyperphosphatemia, frequently observed in chronic kidney disease patients, has been identified as a independent risk factor for cardiovascular disease and mortality. Hyperphosphatemia can be involved in vascular calcification differentiation from vascular smooth muscle cells to osteoblastic cells. In addition, we recently found that hyperphosphatemia causes oxidative stress and inactivation of eNOS in endothelial cells. We have tried to clarify the molecular mechanism and the role of hyperphosphatemia on atherosclerosis.

Recent publications:
Takeda E, et al. A novel function of phosphate-mediated intracellular signal transduction pathways. Adv Enzyme Regul 46:154-161, 2006
Nishida Y, et al. Acute effect of oral phosphate loading on serum fibroblast growth factor 23 levels in healthy men. Kidney Int 70(12): 2141-2147, 2006

Shuto E, et al. Dietary phosphorus acutely impaires endothelial function. J Am Soc Nephrol 20(7): 1504-1512, 2009

Tan VV, et al. Dietary phosphate restriction ameliorates endothelial dysfunction in adenine-induced kidney disease rats. J Clin Biochem Nutr 51: 27-32, 2012

Tanaka S,et al. Dietary phosphate restriction induces hepatic lipid accumulation through dysregulation of cholesterol metabolism in mice. Nutr Res. 2013 Jul;33(7):586-93.

Watari E, et al. Fluctuating plasma phosphorus level by changes in dietary phosphorus intake induces endothelial dysfunction. J Clin Biochem Nutr 56: 35-42, 2015

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5) Nutritional aspects in bone health

Phosphate level mainly regulated by sodium dependent phosphate transporters (NaPi) expressed on kidney and intestine plays an important role for bone health, organ calcification and vitamin D metabolism. The transcriptional mechanism of NaPi-2a, 2b, 2c and vitamin D-1α-hydroxylase gene expression by various hormones and nutrients such as thyroid hormone, vitamin A, vitamin D have been investigated to clarify the homeostasis mechanism of phosphate and vitamin D metabolism.
Bone health is regulated by the balance of osteoblast and osteoclast functions. In order to promote nutritional support, the effects of various nutrients on osteoblast and osteoclast functions were studies. Recent data suggest that quercetinm, Cordyceps sinensis and collagen tripeptide may have positive effects on bone health.

Recent publications:
Yamamoto H, et al: Alternative promoters and renal cell-specific regulation of the mouse type IIa sodium-dependent phosphate cotransporter gene. Biochim Biophys Acta. 1732: 43-52, 2005
Mizuha Y, et al: Water extract of Cordyceps sinensis (WECS) inhibits the RANKL-induced osteoclast differentiation. Biofactors. 30:105-16, 2007

Takei Y, et al. Stanniocalcin 2 is positively and negatively controlled by 1,25(OH)(2)D(3) and PTH in renal proximal tubular cells. J Mol Endocrinol. 2009 Mar;42(3):261-8

Tsuji M, et al. Dietary quercetin inhibits bone loss without effect on the uterus in ovariectomized mice. J Bone Miner Metab. 2009;27(6):673-81

Ishiguro M, et al. Thyroid hormones regulate phosphate homoeostasis through transcriptional control of the renal type IIa sodium-dependent phosphate co-transporter (Npt2a) gene. Biochem J. 2010 Mar 15;427(1):161-9.

Masuda M, et al. Regulation of renal sodium-dependent phosphate co-transporter genes (Npt2a and Npt2c) by all-trans-retinoic acid and its receptors.Biochem J. 2010 Aug 1;429(3):583-92.

Takei Y, et al. Stanniocalcin 2 is associated with ectopic calcification in α-klotho mutant mice and inhibits hyperphosphatemia-induced calcification in aortic vascular smooth muscle cells.Bone. 2012 Apr;50(4):998-1005

Hing NT, et al. Up-regulation of stanniocalcin 1 expression by 1,25-dihydroxy vitamin D(3) and parathyroid hormone in renal proximal tubular cells.J Clin Biochem Nutr. 2012 May;50(3):227-33

Takeda E, Yamamoto H, Yamanaka-Okumura H, Taketani Y.Dietary phosphorus in bone health and quality of life.Nutr Rev. 2012 Jun;70(6):311-21

Kozai M, et al. Thyroid hormones decrease plasma 1α,25-dihydroxyvitamin D levels through transcriptional repression of the renal 25-hydroxyvitamin D3 1α-hydroxylase gene (CYP27B1). Endocrinology. 2013 Feb;154(2):609-22