論文 - 秋枝 さやか
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Continuous Exposure of Nonobese Adult Male Rats to a Soft-Textured, Readily Absorbable Diet Induces Insulin Resistance and Derangements in Hepatic Glucose and Lipid Metabolism. 査読あり
Fumitake Yamaguchi, Sayaka Akieda-Asai, Eriko Nakamura, Hinano Uchida, Atsushi Yamashita, Yukari Date
The Journal of Nutrition 2025年5月
掲載種別：研究論文（学術雑誌）
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Mechanism of muscle atrophy in a normal-weight rat model of type 2 diabetes established by using a soft-pellet diet 査読あり 国際共著
Sayaka Akieda-Asai, Hao Ma, Wanxin Han, Junko Nagata, Fumitake Yamaguchi, Yukari Date
Scientific Reports 2024年4月
担当区分：筆頭著者, 責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌）
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Maternal traits during lactation period reduce the anxiety-related behavior in male offspring: Results from a fostering study in hatano rats 査読あり
Horii Y, Nakajima S, Akieda-Asai S, Ohta R, Kawaguchi M
Physiol Behav 2020年
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Palmitic acid induces guanylin gene expression through the Toll-like receptor 4/nuclear factor-κB pathway in rat macrophages.
Akieda-Asai S, Ma H, Date Y
American journal of physiology. Cell physiology 317 ( 6 ) C1239 - C1246 2019年12月
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Influence of food texture on energy metabolism and adiposity in male rats. 査読あり
Han W, Utoyoma M, Akieda-Asai S, Hidaka A, Yamada C, Hasegawa K, Nunoi H, Date Y
Exp Physiol 103 ( 10 ) 1347 - 1356 2018年10月
記述言語：英語 掲載種別：研究論文（学術雑誌）
DOI： 10.1113/EP087072
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Akieda-Asai S., Ida T., Miyazato M., Kangawa K., Date Y.
Peptides 99 14 - 19 2018年1月
担当区分：筆頭著者 記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Peptides
Recently we found that guanylin (Gn) and its receptor, guanylyl cyclase C (GC-C), are uniquely expressed in the mesenteric macrophages of some diet-resistant rats and that double-transgenic (dTg) rats overexpressing Gn and GC-C in macrophages demonstrate reduced fatty acid synthase and fat accumulation in fat tissue even when fed a high-fat diet (HFD). Lipid accumulation and fatty acid synthase mRNA levels in cocultured dTg rat adipocytes and macrophages were reduced compared with those in adipocytes cultured with WT rat macrophages. Here, we investigated whether Interleukin-15 (IL-15) derived from Gn–GC-C-expressing macrophages regulates lipid accumulation in adipocytes. IL-15 inhibited fatty acid synthase and lipid accumulation via STAT5 in cultured adipocytes. IL-15 mRNA and protein levels in the mesenteric fat of HFD-fed dTg rats were significantly higher than those of HFD-fed WT rats. Phosphorylated STAT5 levels in the mesenteric fat of HFD-fed dTg rats were increased compared with those of HFD-fed WT rats. In addition, the mRNA level of fatty acid synthase in the mesenteric fat was lower in HFD-fed dTg rats than in HFD-fed WT rats. These results support the hypothesis that IL-15 secreted from Gn–GC-C-expressing macrophages contributes to the inhibition of fatty acid synthase and lipid accumulation in adipocytes, leading to obesity resistance.
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Guanylyl cyclase C and guanylin reduce fat droplet accumulation in cattle mesenteric adipose tissue. 査読あり
Yasuda M, Kawabata J, Akieda-Asai S, Nasu T, Date Y
J Vet Sci. 18 ( 3 ) 341 - 348 2017年9月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Utoyama M., Akieda-Asai S., Koda S., Nunoi H., Date Y.
Neuroscience Letters 614 83 - 88 2016年2月
担当区分：筆頭著者 記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Neuroscience Letters
© 2016 Elsevier Ireland Ltd. Recent evidence suggests that neural pathways from the hindbrain to the hypothalamus are important for informing the hypothalamus of the body's condition with regard to energy metabolism. Here we examined energy metabolism in rats with transections of the midbrain that severed the neural pathway from the hindbrain to the hypothalamus, and then investigated the levels of various molecules associated with control of energy metabolism in these rats. Food intake and body weight were higher in the midbrain-transected rats than in sham-operated rats. In addition, the midbrain-transected rats showed insulin resistance and hyperleptinemia. Furthermore, the hypothalamic mRNA levels of anorectic proopiomelanocortin and cocaine- and amphetamine-related transcript were significantly lower in midbrain-transected rats than in sham-operated rats. Our findings elucidate the mechanisms of food intake and energy balance from the perspective of multifactorial regulatory systems that underlie functions such as neurohormonal integration.
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Characterization of inflammatory gene expression and chemotaxis of macrophages guanylin and guanylyl cyclase-C. 査読あり
Hasegawa K, Akieda-Asai S, Date Y
American Journal of Life Sciences 3 ( 3 ) 43 - 47 2015年4月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Hasegawa Kazuya, Akieda-Asai Sayaka, Fujii Yurie, Bae Cho-Rong, Yasuda Masahiro, Date Yukari
Endocrine Journal 62 ( 10 ) 939 - 947 2015年
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：The Japan Endocrine Society
Guanylin (Gn), a bioactive peptide, and its receptor, guanylyl cyclase-C (GC-C), are primarily present in the intestine and maintain homeostasis in body fluids. Recently, rats whose macrophages overexpress Gn and GC-C were found to be resistant to diet-induced obesity. Considering that obesity is strongly related to a chronic inflammatory state in white adipose tissues, it is possible that Gn-GC-C macrophages contribute to the regulation of inflammation. In the present study, we investigated the inflammatory state of mesenteric fat in rats transgenic for both Gn and GC-C (double-transgenic [dTg] rats) by evaluating the levels of cyclic guanosine monophosphate (cGMP), a second messenger of Gn-GC-C, cGMP-dependent protein kinase (PKG), and phosphorylated vasodilator-stimulated phosphoprotein (VASP), a target protein of PKG. The levels of cGMP in dTg rats was higher than in WT rats fed the same diet. Although there were no significant differences in levels of PKG and phosphorylated VASP between WT and dTg rats fed a standard diet (STD), these levels in dTg rats fed a high fat diet (HFD) were markedly increased compared with levels in HFD WT rats. Furthermore, mRNA levels of proinflammatory factors in mesenteric fat were lower in HFD dTg rats than in HFD WT rats and were similar to levels in STD WT and dTg rats. These results indicate that the Gn-GC-C system in macrophages regulates the cGMP-PKG-VASP pathway and controls obesity through the downregulation of proinflammatory factors.
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The short-term effects of soft pellets on lipogenesis and insulin sensitivity in rats. 査読あり
Bae CR*, Hasegawa K*, Akieda-Asai S, Kawasaki Y, Cha YS, Date Y
Preventive Nutrition and Food Science 19 ( 3 ) 164 - 169 2014年9月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Akieda-Asai S., Poleni P., Date Y.
American Journal of Physiology - Endocrinology and Metabolism 306 ( 11 ) 2014年6月
担当区分：筆頭著者 記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：American Journal of Physiology - Endocrinology and Metabolism
CCK and leptin are anorectic hormones produced in the small intestine and white adipose tissue, respectively. Investigating how these hormones act together as an integrated anorectic signal is important for elucidating the mechanisms by which energy balance is maintained. We found here that coadministration of subthreshold CCK and leptin, which individually have no effect on feeding, dramatically reduced food intake in rats. Phosphorylation of AMP-activated protein kinase (AMPK) in the hypothalamus significantly decreased after coinjection of CCK and leptin. In addition, coadministration of these hormones significantly increased mRNA levels of anorectic cocaine- and amphetamineregulated transcript (CART) and thyrotropin-releasing hormone (TRH) in the hypothalamus. The interactive effect of CCK and leptin on food intake was abolished by intracerebroventricular preadministration of the AMPK activator AICAR or anti-CART/anti-TRH antibodies. These findings indicate that coinjection of CCK and leptin reduces food intake via reduced AMPK phosphorylation and increased CART/TRH in the hypothalamus. Furthermore, by using midbrain-transected rats, we investigated the role of the neural pathway from the hindbrain to the hypothalamus in the interaction of CCK and leptin to reduce food intake. Food intake reduction induced by coinjection of CCK and leptin was blocked in midbrain-transected rats. Therefore, the neural pathway from hindbrain to hypothalamus plays an important role in transmitting the anorectic signals provided by coinjection of CCK and leptin. Our findings give further insight into the mechanisms of feeding and energy balance. © 2014 the American Physiological Society.
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Role of the neural pathway from hindbrain to hypothalamus in interaction of GLP1 and leptin in rats
Akieda-Asai S., Poleni P., Hasegawa K., Date Y.
Journal of Endocrinology 220 ( 2 ) 109 - 116 2014年2月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Endocrinology
Glucagon-like peptide-1 (GLP1) and leptin are anorectic hormones. Previously, we have shown that i.p. coadministration of subthreshold GLP1 with leptin dramatically reduced food intake in rats. In this study, by using midbrain-transected rats, we investigated the role of the neural pathway from the hindbrain to the hypothalamus in the interaction of GLP1 and leptin in reducing food intake. Food intake reduction induced by coinjection of GLP1 and leptin was blocked in midbrain-transected rats. These findings indicate that the ascending neural pathway from the hindbrain plays an important role in transmitting the anorectic signals provided by coinjection of GLP1 and leptin. © 2014 Society for Endocrinology.
DOI： 10.1530/JOE-13-0272
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Possible involvement of food texture in insulin resistance and energy metabolism in male rats
Bae C., Hasegawa K., Akieda-Asai S., Kawasaki Y., Senba K., Cha Y., Date Y.
Journal of Endocrinology 222 ( 1 ) 61 - 72 2014年
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Endocrinology
Food texture is known to affect energy metabolism. Although feeding with soft pellets (SP) or via a tube is known to cause increases in body weight, it is unclear how different food textures influence energy metabolism. In this study, we investigated the effects of two different food textures on energy balance and glucose and lipid metabolism in male Wistar rats. The rats were fed SP or control pellets (CP) on a 3-h restricted feeding schedule for 14 weeks and their energy intake, body weight, and energy expenditure were examined. The levels of gastrointestinal hormones, glucose and insulin, were investigated at pre-, mid, and post-feeding. Glucose tolerance and insulin tolerance tests were conducted, and the expressions of molecules involved in the insulin signaling system or lipogenesis in the liver were examined. Histological investigation of pancreatic islets was carried out using anti-insulin and anti-Ki-67 antibodies. Furthermore, the expression in the liver and circulating blood of microRNA-33 (miR-33), which regulates insulin receptor substance 2, was examined. There were no significant differences in energy intake, body weight, or gastrointestinal hormone levels between the SP and CP rats; however, the SP rats showed glucose intolerance and insulin resistance with disruption of insulin signaling. Increases in lipogenic factors and miR-33 expression were also found in the SP rats. The numbers of insulin-positive areas and Ki-67-positive cells of SP rats were significantly increased. This study shows that a soft food texture causes diabetes without obesity, so differences in food texture may be an important factor in type 2 diabetes. © 2014 Society for Endocrinology.
DOI： 10.1530/JOE-13-0553
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Metabolic features of rats resistant to a high-fat diet
Akieda-Asai S., Koda S., Sugiyama M., Hasegawa K., Furuya M., Miyazato M., Date Y.
Obesity Research and Clinical Practice 7 ( 4 ) 2013年7月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Obesity Research and Clinical Practice
Objective: We assessed the metabolic characteristics of high-fat-diet-resistant (DR) rats. Methods: Body weight, energy intake, locomotor activity, oxygen consumption, plasma leptin and lipid levels, size of visceral-fat adipocytes, and mRNA levels of genes related to lipid metabolism were measured in control rats fed standard chow and in obesity-prone (high-fat-diet-induced obesity, DIO) and DR rats fed a high-fat diet. Glucose tolerance and insulin tolerance tests were also performed. Results: DIO rats gained weight more rapidly than did DR and control rats; DR rats gained less weight than did DIO rats despite similar energy intake. Energy expenditure did not differ among the three groups. The diameter of visceral-fat adipocytes was similar in DR and control rats. mRNA levels of genes involved in lipogenesis, such as fatty acid synthase and acetyl-CoA carboxylase, tended to be lower in DR than in control and DIO rats, whereas those of carnitine palmitoyltransferase 1a, which is involved in fatty acid β-oxidation, were greater in DR rats than in the other groups. DIO rats showed hyperinsulinemia and glucose intolerance, whereas DR rats had high sensitivity to insulin. Conclusion: DR rats show suppression of lipogenesis and acceleration of fatty acid β-oxidation in the visceral fat. These characteristics likely contribute to the anti-obesity phenotype of DR rats. © 2013 Asian Oceanian Association for the Study of Obesity.
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Involvement of guanylin and GC-C in rat mesenteric macrophages in resistance to a high-fat diet
Akieda-Asai S., Sugiyama M., Miyazawa T., Koda S., Okano I., Senba K., Poleni P., Hizukuri Y., Okamoto A., Yamahara K., Mutoh E., Aoyama F., Sawaguchi A., Furuya M., Miyazato M., Kangawa K., Date Y.
Journal of Lipid Research 54 ( 1 ) 85 - 96 2013年1月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Lipid Research
A high-fat diet (HFD) is a well-known contributing factor in the development of obesity. Most rats fed HFDs become obese. Those that avoid obesity when fed HFDs are considered diet resistant (DR). We performed a microarray screen to identify genes specific to the mesenteric fat of DR rats and revealed high expression of guanylin and guanylyl cyclase C (GC-C) in some subjects. Our histologic studies revealed that the cellular source of guanylin and GC-C is macrophages. Therefore, we developed double-transgenic (Tg) rats overexpressing guanylin and GC-C in macrophages and found that they were resistant to the effects of HFDs. In the mesenteric fat of HFD-fed Tg rats, Fas and perilipin mRNAs were downregulated, and those of genes involved in fatty acid oxidation were upregulated, compared with the levels in HFD-fed wild-type rats. In vitro studies demonstrated that lipid accumulation was markedly inhibited in adipocytes cocultured with macrophages expressing guanylin and GC-C and that this inhibition was reduced after treatment with guanylin- and GC-C-specific siRNAs. Our results suggest that the macrophagic guanylin-GC-C system contributes to the altered expression of genes involved in lipid metabolism, leading to resistance to obesity. Copyright © 2013 by the American Society for Biochemistry and Molecular Biology, Inc.
DOI： 10.1194/jlr.M029017
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Poleni P., Akieda-Asai S., Koda S., Sakurai M., Bae C., Senba K., Cha Y., Furuya M., Date Y.
Biochemical and Biophysical Research Communications 420 ( 1 ) 36 - 41 2012年3月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Biochemical and Biophysical Research Communications
Glucagon-like peptide-1 (GLP-1) and leptin are anorectic hormones produced in the small intestine and white adipose tissue, respectively. Investigating how these hormones act together as an integrated anorectic signal is important to elucidate a mechanism to maintain energy balance. In the present study, coadministration of subthreshold GLP-1 and leptin dramatically reduced feeding in rats. Although coadministration of GLP-1 with leptin did not enhance leptin signal transduction in the hypothalamus, it significantly decreased phosphorylation of AMP-activated protein kinase (AMPK). In addition, coadministration of GLP-1 with leptin significantly increased proopiomelanocortin (POMC) mRNA levels. Considering that α-melanocortin stimulating hormone (α-MSH) is derived from POMC and functions through the melanocortin-4-receptor (MC4-R) as a key molecule involved in feeding reduction, the interaction of GLP-1 and leptin on feeding reduction may be mediated through the α-MSH/MC4-R system. As expected, the interaction of GLP-1 and leptin was abolished by intracerebroventricular preadministration of the MC4-R antagonists agouti-related peptide and SHU9119. Taken together, GLP-1 and leptin cooperatively reduce feeding at least in part via inhibition of AMPK following binding of α-MSH to MC4-R. © 2012 Elsevier Inc.
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Akieda-Asai S., Ohta R., Shirota M., Jaroenporn S., Watanabe G., Taya K.
Experimental Animals 60 ( 5 ) 509 - 516 2011年11月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Experimental Animals
Hatano high (HAA)- and low (LAA)-avoidance rats were selected from Sprague-Dawley rats genetically on the basis of their active avoidance behavior in a shuttle-box test. The purpose of this study was to investigate stress-related alterations of hormones corticotropin-releasing hormone (CRH), arginine-vasopressin (AVP), prolactin, and adrenocorticotropin (ACTH) in the brain and blood during early avoidance acquisition using two lines of Hatano rats. In paraventricular nucleus (PVN) of the hypothalamus, the CRH levels in HAA rats were significantly increased after shuttle-box tasks compared with before the tasks, whereas the CRH levels in LAA rats significantly decreased after sh uttle-box tasks compared with before the tasks. In the HAA rats, the CRH and AVP levels in the median eminence decreased after shuttle-box tasks, whereas there were no significant differences in the levels between before and after shuttle-box tasks in LAA rats. The plasma concentrations of ACTH were significantly higher in HAA rats than in LAA rats after shuttle-box tasks. These results show that the response of CRH-ACTH was higher in HAA rats than in LAA rats. This phenotype may be an important reason for the high avoidance rates of shuttle-box tasks in HAA rats. These endocrine differences in early avoidance acquisition may be involved in regulation of their avoidance responses in the shuttle-box task.
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Jaroenporn S., Horii Y., Akieda-Asai S., Wang K., Nagaoka K., Ohta R., Shirota M., Watanabe G., Taya K.
Journal of Reproduction and Development 57 ( 6 ) 690 - 699 2011年8月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Reproduction and Development
Hatano high- and low-avoidance rats (HAA and LAA strains, respectively) were selected and bred according to the avoidance rate in a shuttle-box task. Although they have clear strain differences in ovarian function, their endocrine mechanisms still remain to be clarified. Differences in female reproductive endocrinology between the strains were investigated by means of measuring the plasma concentration of reproductive hormones during the estrous cycle. LAA rats showed approximately threefold lower basal and surge levels of LH, a more than fourfold lower level of FSH surges and higher levels of inhibin A and inhibin B during the estrous cycle compared with the levels seen in HAA rats. The concentration of estradiol-17β in the proestrous stage was significantly lower in LAA rats than in HAA rats. Additionally, LH and FSH secretions from primary cultured anterior pituitary cells with or without in vitro GnRH stimulation were lower in the cells derived from LAA rats and, in terms of FSH secretion, were unresponsive to GnRH in contrast to cells derived from HAA rats. Although an increased number of preantral follicles in diestrus were observed in LAA rats, number of hCG-induced ovulation was lower in LAA rats. LAA rats may have much more follicle growth during the early stage of folliculogenesis, but most follicles might not grow into mature follicles. These results strongly suggest that the strain difference in ovarian function of these two Hatano rats is due to the difference in the regulation of hypothalamo-hypophyseal system for gonadotropins secretion. © 2012 Society for Reproduction and Development.
DOI： 10.1262/jrd.10-160S
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Sex differences in energy metabolism in pre-pubescent, early pubescent and adult rats
Mutoh E., Senba K., Akieda-Asai S., Miyashita A., Poleni P., Date Y.
Obesity Research and Clinical Practice 5 ( 2 ) 2011年4月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Obesity Research and Clinical Practice
Objective: This study was intended to investigate sex differences in response to a high fat (HF) diet at three stages, pre-puberty, early puberty, and adulthood. Methods: Body weight, energy intake, glucose, insulin, and leptin concentrations were measured in male and female rats that were fed either a HF or a control chow during each stage of development. The sex hormones of adult rats were also examined. In addition, metabolic factors of male rats pair-fed with females were evaluated. Results: At pre-puberty, the average body weight of pups born to a HF dam exceeded that of the control, whereas there were no significant differences in body weight between males and females. During early puberty and among 15-wk-old rats, males exhibited greater weight gain with higher energy intake than did females. During all three stages, HF rats exhibited significant increases in body weight, insulin and leptin concentrations. Estradiol levels of females were higher than those of males, and those of the HF groups were significantly lower than the control groups. Although the body weight gain in male rats pair-fed with females exceeded that of the females, the insulin and leptin levels of pair-fed HF males decreased to the control levels. Conclusion: HF male rats became obese earlier than HF females. This result may be the result of differences in estradiol levels between males and females. The decline of insulin and leptin levels in pair-fed male groups indicates that caloric restriction among male rats could reduce the incidence of metabolic diseases. © 2010 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.