Gender Differences in Metabolic Disorders and Related Diseases in Spontaneously Diabetic Torii-LeprfaRats

Ohta, Takeshi; Katsuda, Yoshiaki; Miyajima, Katsuhiro; Sasase, Tomohiko; Kimura, Shuichi; Tong, Bin; Yamada, Takahisa

doi:10.1155/2014/841957

Cited by 36 publications

(27 citation statements)

References 30 publications

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“…The risk of obesity-related comorbidities is well established in men, but less so for age matched pre-menopausal women [6]. There are a number of experimental and clinical studies showing sex differences in the susceptibility to various diseases like IR, T2DM and metabolic syndrome [7][8][9][10][11]. Moreover, CVD develops earlier and are more frequently in men compared with premenopausal women [12].…”

Section: Introductionmentioning

confidence: 99%

Influence of a High-Fat Diet on Cardiac iNOS in Female Rats

Jovanović

Sudar-Milovanović

Obradović

et al. 2017

CVP

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Overexpression of inducible nitric oxide synthase (iNOS) is a key link between high-fat (HF) diet induced obesity and cardiovascular (CV) disease. Several studies have reported that oestradiol has cardioprotective effects that may be mediated through reduction of iNOS activity/expression. In the present study, female Wistar rats were fed a standard diet or a HF diet (balanced diet for laboratory rats enriched with 42% fat) for 10 weeks. Gene and protein expression of iNOS were measured in heart tissue. HF diet-fed rats exhibited a significant increase in cardiac iNOS mRNA by 695% (p<0.05), iNOS protein level by 248% (p<0.01), without changes in nitrate/nitrite levels. Expression of CD36 protein in plasma membranes was increased by 37% (p<0.05), while the concentration of free fatty acids (FFA) was reduced by 25% (p<0.01) in HF diet-fed rats. Expression of the p50 subunit of nuclear factor-κB (NFκB-p50) in heart lysate was increased by 77% (p<0.01) in HF diet-fed rats.Expression and phosphorylation of protein kinase B (Akt) and extracellular signal-regulated kinases 1/2 (ERK1/2) in control and HF diet-fed rats were also examined. Expression of Akt and ERK1/2 were unchanged between the groups. There was a significant increase in the ratio of phospho-Akt/total Akt but not for phospho-ERK1/2/total ERK1/2/ in HF-fed rats.Estrogen receptor-α levels (by 50%; p<0.05) and serum oestradiol concentrations (by 35%; p<0.05) were examined and shown to be significantly reduced in HF diet-fed rats. Our results revealed that a HF diet led to increased iNOS expression, most likely via a mechanism involving Akt and NFκB-p50 proteins. Decreased levels of oestradiol and ERα protein in the HF-fed group, in combination with increased iNOS levels are consistent with the hypothesis that oestradiol has a cardioprotective effect through its ability to regulate iNOS expression.Key words: cardioprotection, cardiovascular disease, oestradiol, inducible nitric oxide synthase, obesity Abbreviations: Akt, protein kinase B; CD36, cluster of differentiation 36; CHD, coronary heart disease; CV, cardiovascular; CVD, cardiovascular disease; DMT2, diabetes mellitus type 2; ERα, oestrogen receptor-α; ERs, oestrogen receptors; ERK1/2, extracellular signalregulated kinases 1/2; FFA, free fatty acids; HF, high fat; HOMA-IR, HOMA-index of insulin resistance; HOMA-β, HOMA-index of β-cell function; IκB, inhibitor of NFκB; iNOS, inducible nitric oxide synthase; IR, insulin resistance; NFκB-p50, the p50 subunit of nuclear factor-κB; TES, N-[Tris(hydroxymethyl)methyl]-2-aminoethanesulfonic acid; TG, triglycerides VSMCs, vascular smooth muscle cells.

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Section: Introductionmentioning

confidence: 99%

Influence of a High-Fat Diet on Cardiac iNOS in Female Rats

Jovanović

Sudar-Milovanović

Obradović

et al. 2017

CVP

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“…However, if premenopausal women are compared with age-matched men, the differences are striking (6,50). In rodents, a sexual dimorphism in T2DM development can also be observed (37,39). The New Zealand obese (NZO) mouse, a model of polygenic obesity and T2DM (25), shows that females are protected from T2DM unless they are fed an extremely high-fat diet (40,52).…”

mentioning

confidence: 99%

Diabetes prevalence in NZO females depends on estrogen action on liver fat content

Lubura

Hesse

Kræmer

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

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In humans and rodents, risk of metabolic syndrome is sexually dimorphic, with an increased incidence in males. Additionally, the protective role of female gonadal hormones is ostensible, as prevalence of type 2 diabetes mellitus (T2DM) increases after menopause. Here, we investigated the influence of estrogen (E2) on the onset of T2DM in female New Zealand obese (NZO) mice. Diabetes prevalence (defined as blood glucose levels >16.6 mmol/l) of NZO females on high-fat diet (60 kcal% fat) in week 22 was 43%. This was markedly dependent on liver fat content in week 10, as detected by computed tomography. Only mice with a liver fat content >9% in week 10 plus glucose levels >10 mmol/l in week 9 developed hyperglycemia by week 22. In addition, at 11 wk, diacylglycerols were elevated in livers of diabetes-prone mice compared with controls. Hepatic expression profiles obtained from diabetes-prone and -resistant mice at 11 wk revealed increased abundance of two transcripts in diabetes-prone mice: Mogat1, which catalyzes the synthesis of diacylglycerols from monoacylglycerol and fatty acyl-CoA, and the fatty acid transporter Cd36. E2 treatment of diabetes-prone mice for 10 wk prevented any further increase in liver fat content and reduced diacylglycerols and the abundance of Mogat1 and Cd36, leading to a reduction of diabetes prevalence and an improved glucose tolerance compared with untreated mice. Our data indicate that early elevation of hepatic Cd36 and Mogat1 associates with increased production and accumulation of triglycerides and diacylglycerols, presumably resulting in reduced hepatic insulin sensitivity and leading to later onset of T2DM.

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“…In this study, the SDT fatty rats were hyperlipidaemic, suggesting that hyperlipidaemia could cause the reduction of PT and APTT in SDT fatty rats, which might contribute to lower blood flow. Ohta et al reported gender differences with respect to metabolic disorders in SDT fatty rats; female rats showed more severe insulin resistance and hyperlipidaemia than male rats . Therefore, female SDT fatty rats could show a marked reduction in PT and APTT, which could lead to severe blood flow reduction.…”

Section: Discussionmentioning

confidence: 99%

Analysis of haemodynamics and angiogenic response to ischaemia in the obese type 2 diabetic model Spontaneously Diabetic Torii Lepr^fa (SDT fatty) rats

Murai

Sasase

Tadaki

et al. 2020

Clin Exp Pharma Physio

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Peripheral artery disease (PAD) is defined as peripheral blood flow impairment, especially in the legs, caused by atherosclerotic stenosis. The disease decreases quality of life because of intermittent claudication or necrosis of the leg. The hindlimb ischaemia model, in which ischaemia is induced by femoral artery ligation, is often utilized as a PAD model. In the hindlimb ischaemia model, nonmetabolic syndrome animals are mainly used. In this study, we investigated the usefulness of Spontaneously Diabetic Torii Leprfa (SDT fatty) rats, a new model for obese type 2 diabetes, as a new PAD animal model. We found that hindlimb blood flow in SDT fatty rats was significantly lower than that in Sprague–Dawley (SD) rats under nonischaemic conditions. Furthermore, SDT fatty rats showed a significantly higher plasma nitrogen oxide level, shorter prothrombin time, and shorter activated partial thromboplastin time than SD rats. In addition, we found that the change in blood flow 7 days after induction of hindlimb ischaemia and the number of Von Willebrand factor‐positive vessels in gastrocnemius muscles were significantly lower in SDT fatty rats than in SD rats. These results suggest that excess production of reactive oxygen species and coagulation activation could be involved in lower blood flow in non‐ischaemic rats and that decreased angiogenesis could be involved in the poor recovery of blood flow in SDT fatty rats with hindlimb ischaemia. Taken together, our results suggest that SDT fatty rats might be useful as a new model for PAD with metabolic syndrome.

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Gender Differences in Metabolic Disorders and Related Diseases in Spontaneously Diabetic Torii-Lepr^faRats

Cited by 36 publications

References 30 publications

Influence of a High-Fat Diet on Cardiac iNOS in Female Rats

Influence of a High-Fat Diet on Cardiac iNOS in Female Rats

Diabetes prevalence in NZO females depends on estrogen action on liver fat content

Analysis of haemodynamics and angiogenic response to ischaemia in the obese type 2 diabetic model Spontaneously Diabetic Torii Lepr^fa (SDT fatty) rats

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Gender Differences in Metabolic Disorders and Related Diseases in Spontaneously Diabetic Torii-LeprfaRats

Cited by 36 publications

References 30 publications

Influence of a High-Fat Diet on Cardiac iNOS in Female Rats

Influence of a High-Fat Diet on Cardiac iNOS in Female Rats

Diabetes prevalence in NZO females depends on estrogen action on liver fat content

Analysis of haemodynamics and angiogenic response to ischaemia in the obese type 2 diabetic model Spontaneously Diabetic Torii Leprfa (SDT fatty) rats

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Gender Differences in Metabolic Disorders and Related Diseases in Spontaneously Diabetic Torii-Lepr^faRats

Analysis of haemodynamics and angiogenic response to ischaemia in the obese type 2 diabetic model Spontaneously Diabetic Torii Lepr^fa (SDT fatty) rats