Possible Involvement of Hypothalamic Nucleobindin-2 in Hyperphagic Feeding in Tsumura Suzuki Obese Diabetes Mice

Miyata, Shigeo; Yamada, Naohito; Kawada, Toru

doi:10.1248/bpb.b12-00505

Cited by 19 publications

(20 citation statements)

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“…1b), indicating that TSOD mice already developed hypercholesterolemia at 5 weeks of age. Although non-fasting blood glucose level in TSOD mice at 11 weeks of age was significantly higher than that in age-matched TSNO mice, as reported previously, (7) no significant difference in glucose level was found between TSNO and TSOD mice at 5 weeks of age (Fig. 1c).…”

Section: Resultssupporting

confidence: 85%

“…1a), consistent with a previous report. (7) Weight gain in TSOD mice during the period between 5 and 11 weeks of age was much greater than that in TSNO mice during the same period, indicating that the progression of obesity is rapid in TSOD mice compared with TSNO mice. Whereas plasma total cholesterol levels in TSOD mice at 5 and 11 weeks of age were significantly higher than those in age-matched TSNO mice, no significant difference was observed between TSOD mice at 5 and 11 weeks of age (Fig.…”

Section: Resultsmentioning

confidence: 85%

“…(5) TSOD mice developed obesity, hyperphagia, hyperinsulinemia, and hyperleptinemia before developing the diabetic phenotypes, compared with age-matched control Tsumura Suzuki Non-Obese (TSNO) mice. (5–7) Several diabetes-related phenotypes, including hypertriglyceridemia, hypercholesterolemia, impaired glucose tolerance, insulin resistance, impaired insulin secretion, and hyperglycemia, were apparently observed in TSOD mice older than around 11 weeks of age. (5–8) It is suggested that the insulin resistance in TSOD mice is partly due to the impairment of insulin-stimulated translocation of glucose transporter type 4 (GLUT4).…”

Section: Introductionmentioning

confidence: 99%

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Type 2 diabetes model TSOD mouse is exposed to oxidative stress at young age

Murotomi¹,

Umeno²,

Yasunaga³

et al. 2014

J. Clin. Biochem. Nutr.

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Tsumura Suzuki Obese Diabetes (TSOD) mouse, a model of obese type 2 diabetes, older than around 11 weeks of age develops diabetic phenotypes. Previous studies have indicated that the development of diabetes is partly due to three loci associated with body weight and glucose homeostasis. However, little is known about the initial events triggering the development of the diabetic phenotypes in TSOD mouse. Here, we investigated the alteration of diabetes-related parameters, including the levels of blood glucose and inflammatory cytokines, and the oxidative stress status, in young TSOD mice. TSOD mice at 5 weeks of age showed increases in body weight and plasma total cholesterol level, but not hyperglycemia or impaired glucose tolerance, compared with age-matched control Tsumura Suzuki Non-Obese (TSNO) mice. Plasma tumor necrosis factor (TNF)-α and interleukin (IL)-6 were not detected in TSOD mice at 5 weeks of age. However, plasma total hydroxyoctadecadienoic acid (tHODE), a biomarker of oxidative stress, was increased in TSOD mice relative to TSNO mice at same age. The results demonstrated that young TSOD mice are exposed to oxidative stress before developing the diabetic phenotypes, and suggested that oxidative stress is an initial event triggering the development of diabetes in TSOD mice.

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Section: Resultssupporting

confidence: 85%

Section: Resultsmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

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Type 2 diabetes model TSOD mouse is exposed to oxidative stress at young age

Murotomi¹,

Umeno²,

Yasunaga³

et al. 2014

J. Clin. Biochem. Nutr.

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“…In rodents, fasting decreased NUCB2/nesfatin-1 expression in the PVN [3], whereas refeeding increased the number of nesfatin-1-immunopositive neurons and NUCB2 mRNA in the SON [31]. Miyata et al [32] have reported that hypothalamic NUCB2 mRNA and protein levels were significantly reduced in mouse obesity models compared to controls. However, it is unknown whether such an association exists in humans.…”

Section: Introductionmentioning

confidence: 99%

Nucleobindin-2/Nesfatin-1 in the Human Hypothalamus Is Reduced in Obese Subjects and Colocalizes with Oxytocin, Vasopressin, Melanin-Concentrating Hormone, and Cocaine- and Amphetamine-Regulated Transcript

Psilopanagioti

Nikou

Papadaki³

2019

Neuroendocrinology

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Background/Aims: Nesfatin-1, processed from nucleobindin-2 (NUCB2), is a potent anorexigenic peptide being expressed in rodent hypothalamic nuclei and involved in the regulation of feeding behavior and body weight in animals. The present study aimed to investigate NUCB2/nesfatin-1 protein expression in the human hypothalamus as well as its correlation with body weight. Methods: Sections of hypothalamus and adjacent cholinergic basal forebrain nuclei, including the nucleus basalis of Meynert (NBM) and the diagonal band of Broca (DBB), from 25 autopsy cases (17 males, 8 females; 8 lean, 9 overweight, 8 obese) were examined using immunohistochemistry and double immunofluorescence labeling. Results: Prominent NUCB2/nesfatin-1 immunoexpression was detected in supraoptic, paraventricular, and infundibular nuclei, lateral hypothalamic area (LHA)/perifornical region, and NBM/DBB. NUCB2/nesfatin-1 was found to extensively colocalize with (a) oxytocin and vasopressin in paraventricular and supraoptic nuclei, (b) melanin-concentrating hormone in the LHA, and (c) cocaine- and amphetamine-regulated transcript in infundibular and paraventricular nuclei and LHA. Interestingly, in the LHA, NUCB2/nesfatin-1 protein expression was significantly decreased in obese, compared with lean (p < 0.01) and overweight (p < 0.05) subjects. Conclusions: The findings of the present study are suggestive of a potential role for NUCB2/nesfatin-1 as an integral regulator of food intake and energy homeostasis in the human hypothalamus. In the LHA, an appetite- and reward-related brain area, reduced NUCB2/nesfatin-1 immunoexpression may contribute to dysregulation of homeostatic and/or hedonic feeding behavior and obesity. NUCB2/nesfatin-1 localization in NBM/DBB might imply its participation in the neuronal circuitry controlling cognitive influences on food intake and give impetus towards unraveling additional biological actions of NUCB2/nesfatin-1 in human neuronal networks.

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“…This hypothesis is supported by the observation that TSOD mice dramatically gain weight around 5 weeks of age and the rate of weight gain is similar to that of TSNO mice after 5 weeks of age. 10,29) In the period, obesity is mainly developed by overeating which is caused by hypothalamic neuropeptides and the properties of adipocytes may syner- gistically promote the development of obesity. It will lead to development of T2DM.…”

Section: Discussionmentioning

confidence: 99%

Activation of PPARγ at an Early Stage of Differentiation Enhances Adipocyte Differentiation of MEFs Derived from Type II Diabetic TSOD Mice and Alters Lipid Droplet Morphology

Ishibashi

Takeda

Nakatani

et al. 2017

Biological & Pharmaceutical Bulletin

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Type 2 diabetic Tsumura, Suzuki, obese, diabetes (TSOD) mice gradually gain weight as compared to corresponding Tsumura, Suzuki, non-obesity (TSNO) control mice, and develop insulin resistance. Although development of type 2 diabetes mellitus is associated with dysfunction of adipocytes, little is known about the properties of adipocytes from TSOD mice. Therefore, we attempted to remove intracorporeal factors and elucidate inherent properties of adipocytes of TSOD mice using adipocytes differentiated from mouse embryonic fibroblasts ( Key words adipocyte; differentiation; obesity; peroxisome proliferator-activated receptor-γ (PPARγ); rosiglitazone; Tsumura, Suzuki, obese, diabetes (TSOD) mouseThe worldwide population with type 2 diabetes mellitus (T2DM) is increasing, and the number of patients reached 415 million in 2015.1) Since T2DM is associated with vascular and other end-organ disease, 2) prevention of T2DM is a major public health issue. It is well known that obesity is a major risk factor for T2DM.3) Notably, incident of T2DM is correlated with abdominal visceral adipose tissue mass in humans.4) Therefore, understanding of roles of adipose tissue in the development of T2DM may lead to better methods for prevention of T2DM.Adipose tissue plays important roles in energy storage and release, and secretes various cytokines. Previous studies show that adipose-specific knockout of mitochondrial transcription factor A enhances energy expenditure and protects from dietinduced obesity and insulin resistance in mice.5) Moreover, adipose-specific glucose transporter type 4 (GLUT4) knockout mice exhibit insulin resistance and diabetes via secretion of retinol binding protein-4. 6) Thus, adipose functions are closely associated with the development of insulin resistance and T2DM. However, since T2DM is a complex illness resulting from a variety of genetic and environmental factors, single gene knockout mice provide limited information on the roles of adipose tissue in the development of T2DM. Therefore, more suitable model of human T2DM have been needed for such a kind of research.In 1992, the Tsumura, Suzuki, obese, diabetes (TSOD) mouse has been established as an animal model of human T2DM by the selective breeding of male mice of ddY strain with heavy body and urinary glucose.7) The mice exhibit overeating and gradually gain weight as compared to corresponding control mice, Tsumura, Suzuki, non-obesity (TSNO), and high blood glucose and urinary glucose are frequently observed in male mice of TSOD. Quantitative trait locus (QTL) analysis reveal that body weight and blood glucose levels in male mice of TSOD are affected by combination of multiple genetic loci (e.g., NIDD4,5,6).8) Several studies examine the roles of adipose tissue in development of T2DM using the mice and show that insulin-dependent glucose uptake 9) and GLUT4 translocation to the plasma membrane 10) is impaired in the adipose tissue. However, since these properties may be developed by various intracorporeal factors such as hormones and cytokines, t...

show abstract

Possible Involvement of Hypothalamic Nucleobindin-2 in Hyperphagic Feeding in Tsumura Suzuki Obese Diabetes Mice

Cited by 19 publications

References 56 publications

Type 2 diabetes model TSOD mouse is exposed to oxidative stress at young age

Type 2 diabetes model TSOD mouse is exposed to oxidative stress at young age

Nucleobindin-2/Nesfatin-1 in the Human Hypothalamus Is Reduced in Obese Subjects and Colocalizes with Oxytocin, Vasopressin, Melanin-Concentrating Hormone, and Cocaine- and Amphetamine-Regulated Transcript

Activation of PPARγ at an Early Stage of Differentiation Enhances Adipocyte Differentiation of MEFs Derived from Type II Diabetic TSOD Mice and Alters Lipid Droplet Morphology

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