Plasma Glucagon and Free Fatty Acid Responses to a Glucose Load in the Obese Spontaneous Hypertensive Rat (SHROB) Model of Metabolic Syndrome X

Velliquette, Rodney A.; Koletsky, Richard J.; Ernsberger, Paul

doi:10.1177/153537020222700303

Cited by 24 publications

(30 citation statements)

References 39 publications

(38 reference statements)

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“…It has already been reported (Velliquette et al 2002) that SHROB, despite fasting normoglycemia, are hyperinsulinemic and glucose intolerant compared with WKY animals.…”

Section: Discussionmentioning

confidence: 99%

“…Body weight results were expressed compared with food intake, by using the following formula: food intake (g)/body weight (g)!100. Oral glucose tolerance tests were carried out at the end of the treatment period as described previously (Ernsberger et al 1999b, Velliquette et al 2002, Velliquette & Ernsberger 2003. All rats were fasted for 18 h and administered a 50% glucose solution in water by gavages at a dose of 6 g/kg body weight.…”

Section: Animalsmentioning

confidence: 99%

See 1 more Smart Citation

Effects of aglycone genistein in a rat experimental model of postmenopausal metabolic syndrome

Bitto

Altavilla²,

Bonaiuto³

et al. 2008

Journal of Endocrinology

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Genistein aglycone, a soy derived isoflavone, has been demonstrated to be effective in reducing cardiovascular risk in postmenopausal women. We therefore investigated its effects in an experimental model of postmenopausal metabolic syndrome. Female spontaneously hypertensive obese rats (SHROB, nZ40), a genetic model of syndrome X, and age-matched Wistar Kyoto (WKY, nZ40) rats were used. A group of SHROB (nZ20) and WKY (nZ20) animals were ovariectomized (OVX). Four weeks after surgery all animals were randomized to receive either genistein (54 mg/human equivalent dose/day for 4 weeks), or vehicle. Body weight, food intake, systolic blood pressure (SBP), heart rate, plasma glucose, insulin resistance (HOMA-IR), total plasma cholesterol and triglycerides, and uterine weights were studied. Furthermore, we investigated acetylcholine-and sodium nitroprussideinduced relaxation of aortic rings as well as NG-L-arginine (L-NMA: 10-100 mM) induced vasoconstriction in phenylephrine-precontracted aortic segments. Liver expression of the peroxisome proliferator-activated receptor alpha (PPARA and gamma (PPARG was also assessed. OVX animals had a slight increase in SBP, body weight, insulin resistance, and plasma cholesterol. OVX-SHROB rats showed also impaired endothelial responses, blunted L-NMA induced contraction (L-NMA 100 mM, WKYZ 2 . 2G0 . 3 g/mg tissue; OVX-SHROBZ1 . 1G0 . 4 g/mg tissue). Genistein treatment decreased SBP and plasma lipids, ameliorated endothelial dysfunction and insulin resistance, increased HDL cholesterol, and enhanced liver expression of PPARA and PPARG. Our data suggest that genistein is effective in ameliorating cardiovascular profiles in an experimental model of postmenopausal metabolic syndrome, attenuating the features of this disease. The effects of genistein are likely mediated by PPARA and PPARG receptors. This evidence would support the rationale for some pilot clinical trials using genistein in postmenopausal women affected by metabolic syndrome.

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“…It has already been reported (Velliquette et al 2002) that SHROB, despite fasting normoglycemia, are hyperinsulinemic and glucose intolerant compared with WKY animals.…”

Section: Discussionmentioning

confidence: 99%

Section: Animalsmentioning

confidence: 99%

Effects of aglycone genistein in a rat experimental model of postmenopausal metabolic syndrome

Bitto

Altavilla²,

Bonaiuto³

et al. 2008

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…Although naturally occurring rodent models resembling human metabolic syndrome such as Zucker diabetic fatty (ZDF) (62) and obese spontaneous hypertensive (SHROB) rats (63) have been characterized, the pathophysiologic relationship between hypertension and the metabolic syndrome in these models remains incompletely understood. Moreover, it is important to note that diet-induced obese models, even accompanied by hyperleptinemia and hyperinsulinemia, do not necessarily have hypertension (64,65).…”

Section: Discussionmentioning

confidence: 99%

Transgenic amplification of glucocorticoid action in adipose tissue causes high blood pressure in mice

Masuzaki¹,

Yamamoto²,

Kenyon³

et al. 2003

J. Clin. Invest.

392

122

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Obesity is closely associated with the metabolic syndrome, a combination of disorders including insulin resistance, diabetes, dyslipidemia, and hypertension. A role for local glucocorticoid reamplification in obesity and the metabolic syndrome has been suggested. The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates active cortisol from inactive 11-keto forms, and aP2-HSD1 mice with relative transgenic overexpression of this enzyme in fat cells develop visceral obesity with insulin resistance and dyslipidemia. Here we report that aP2-HSD1 mice also have high arterial blood pressure (BP). The mice have increased sensitivity to dietary salt and increased plasma levels of angiotensinogen, angiotensin II, and aldosterone. This hypertension is abolished by selective angiotensin II receptor AT-1 antagonist at a low dose that does not affect BP in non-Tg littermates. These findings suggest that activation of the circulating renin-angiotensin system (RAS) develops in aP2-HSD1 mice. The longterm hypertension is further reflected by an appreciable hypertrophy and hyperplasia of the distal tubule epithelium of the nephron, resembling salt-sensitive or angiotensin II-mediated hypertension. Taken together, our findings suggest that overexpression of 11β-HSD1 in fat is sufficient to cause saltsensitive hypertension mediated by an activated RAS. The potential role of adipose 11β-HSD1 in mediating critical features of the metabolic syndrome extends beyond obesity and metabolic complications to include the most central cardiovascular feature of this disorder. Conflict of interest:The authors have declared that no conflict of interest exists. Nonstandard abbreviations used: arterial blood pressure (BP); angiotensinogen (AGT); renin-angiotensin system (RAS); transgenic (Tg); 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1); adipocyte fatty acid binding protein (aP2); heart rate (HR); mean arterial pressure (MAP); angiotensin II receptor AT-1 (AT-1 receptor); radioimmunoassay (RIA).

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“…Several substrains of SHROB rats with diverse severity of symptoms are used (Russell & Proctor 2006, de Artiñano & Castro 2009). SHROB rats can be identified as obese at about 5 weeks of age together with hyperinsulinemia, slightly elevated blood glucose (Friedman et al 1997), and insulin resistance (Velliquette et al 2002). Spontaneous hypertension usually occurs at w3 months of age and rises progressively; animals also develop cardiac hypertrophy and vascular disease (Ernsberger et al 2007).…”

Section: Rat Models Of Obesity and Hypertensionmentioning

confidence: 99%

Obesity-related hypertension: possible pathophysiological mechanisms

Vaněčková¹,

Maletı́nská²,

Behuliak³

et al. 2014

Journal of Endocrinology

128

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Hypertension is one of the major risk factors of cardiovascular diseases, but despite a century of clinical and basic research, the discrete etiology of this disease is still not fully understood. The same is true for obesity, which is recognized as a major global epidemic health problem nowadays. Obesity is associated with an increasing prevalence of the metabolic syndrome, a cluster of risk factors including hypertension, abdominal obesity, dyslipidemia, and hyperglycemia. Epidemiological studies have shown that excess weight gain predicts future development of hypertension, and the relationship between BMI and blood pressure (BP) appears to be almost linear in different populations. There is no doubt that obesity-related hypertension is a multifactorial and polygenic trait, and multiple potential pathogenetic mechanisms probably contribute to the development of higher BP in obese humans. These include hyperinsulinemia, activation of the renin-angiotensin-aldosterone system, sympathetic nervous system stimulation, abnormal levels of certain adipokines such as leptin, or cytokines acting at the vascular endothelial level. Moreover, some genetic and epigenetic mechanisms are also in play. Although the full manifestation of both hypertension and obesity occurs predominantly in adulthood, their roots can be traced back to early ontogeny. The detailed knowledge of alterations occurring in the organism of experimental animals during particular critical periods (developmental windows) could help to solve this phenomenon in humans and might facilitate the age-specific prevention of human obesity-related hypertension. In addition, better understanding of particular pathophysiological mechanisms might be useful in so-called personalized medicine. Key Words" obesity " hypertension " sympathetic nervous system " renin-angiotensin system " critical developmental periods " epigenetics " rat

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Plasma Glucagon and Free Fatty Acid Responses to a Glucose Load in the Obese Spontaneous Hypertensive Rat (SHROB) Model of Metabolic Syndrome X

Cited by 24 publications

References 39 publications

Effects of aglycone genistein in a rat experimental model of postmenopausal metabolic syndrome

Effects of aglycone genistein in a rat experimental model of postmenopausal metabolic syndrome

Transgenic amplification of glucocorticoid action in adipose tissue causes high blood pressure in mice

Obesity-related hypertension: possible pathophysiological mechanisms

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