Changes in hepatic protein expression in spontaneously hypertensive rats suggest early stages of non-alcoholic fatty liver disease

Svoboda, Devon S.; Kawaja, Michael D.

doi:10.1016/j.jprot.2011.12.011

Cited by 16 publications

(13 citation statements)

References 77 publications

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“…Therefore, it is possible that this deficiency is compensated by the higher Bmal2 sensitivity in SHR. The latter possibility of a higher metabolic pressure on the clock in SHR is supported by the previously demonstrated relationship between hypertension and hepatic physiology, as manifested by the metabolic aberrances of SHRs [32] and the differences in the expression of metabolism-relevant proteins in SHR liver [52], as well as by the different sensitivity of the metabolic markers to RF, as discussed below.…”

Section: Discussionmentioning

confidence: 73%

Increased Sensitivity of the Circadian System to Temporal Changes in the Feeding Regime of Spontaneously Hypertensive Rats - A Potential Role for Bmal2 in the Liver

et al. 2013

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The mammalian timekeeping system generates circadian oscillations that rhythmically drive various functions in the body, including metabolic processes. In the liver, circadian clocks may respond both to actual feeding conditions and to the metabolic state. The temporal restriction of food availability to improper times of day (restricted feeding, RF) leads to the development of food anticipatory activity (FAA) and resets the hepatic clock accordingly. The aim of this study was to assess this response in a rat strain exhibiting complex pathophysiological symptoms involving spontaneous hypertension, an abnormal metabolic state and changes in the circadian system, i.e., in spontaneously hypertensive rats (SHR). The results revealed that SHR were more sensitive to RF compared with control rats, developing earlier and more pronounced FAA. Whereas in control rats, the RF only redistributed the activity profiles into two bouts (one corresponding to FAA and the other corresponding to the dark phase), in SHR the RF completely phase-advanced the locomotor activity according to the time of food presentation. The higher behavioral sensitivity to RF was correlated with larger phase advances of the hepatic clock in response to RF in SHR. Moreover, in contrast to the controls, RF did not suppress the amplitude of the hepatic clock oscillation in SHR. In the colon, no significant differences in response to RF between the two rat strains were detected. The results suggested the possible involvement of the Bmal2 gene in the higher sensitivity of the hepatic clock to RF in SHR because, in contrast to the Wistar rats, the rhythm of Bmal2 expression was advanced similarly to that of Bmal1 under RF. Altogether, the data demonstrate a higher behavioral and circadian responsiveness to RF in the rat strain with a cardiovascular and metabolic pathology and suggest a likely functional role for the Bmal2 gene within the circadian clock.

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Section: Discussionmentioning

confidence: 73%

Increased Sensitivity of the Circadian System to Temporal Changes in the Feeding Regime of Spontaneously Hypertensive Rats - A Potential Role for Bmal2 in the Liver

et al. 2013

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“…However, these reports are limited due to their dependence on comparing SHRs and normotensive WKY rats, which are clearly different despite having a similar origin (11). By contrast, we adjusted blood pressure using 2 salt levels in the SHR model.…”

Section: Cdaa Diet --------------------------------------------------mentioning

confidence: 99%

“…SHRs and WKY rats both originate from Wistar rats, but they diverged Hypertension exacerbates liver injury and hepatic fibrosis induced by a choline-deficient L-amino acid-defined diet in rats SHIHO sufficiently long ago to now be essentially separate background strains (11). This is a limitation of the comparison of effects in these 2 types of rats.…”

Section: Introductionmentioning

confidence: 99%

“…This is a limitation of the comparison of effects in these 2 types of rats. In addition, several proteins differ in the livers of SHRs and WKY rats, including proteins that induce oxidative stress (11). For this reason, we investigated the effects of hypertension induced by a high-salt diet on the severity of hepatic steatosis, liver injury and hepatic fibrosis induced by a CDAA diet in the SHR model.…”

Section: Introductionmentioning

confidence: 99%

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Hypertension exacerbates liver injury and hepatic fibrosis induced by a choline-deficient L-amino acid-defined diet in rats

Arima

Uto

Ibusuki

et al. 2013

International Journal of Molecular Medicine

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Abstract. The effect of hypertension on non-alcoholic fatty liver disease (NAFLD) remains unclear at the molecular level. In this study, we investigated the effects of hypertension on the degree of hepatic steatosis, liver injury and hepatic fibrosis induced by a choline-deficient L-amino acid-defined (CDAA) diet in spontaneously hypertensive rats (SHRs). Seven-week-old male SHRs were fed standard chow with high or normal salt concentrations for 7 weeks, followed by a CDAA diet containing high or normal salt for an additional 8 or 24 weeks. Hepatic steatosis was assessed using hepatic triglyceride levels and Oil red O staining. Hepatic fibrosis was evaluated using Sirius red and Azan staining. Systolic blood pressure (SBP) gradually increased with a high-salt diet and was significantly higher after 7 weeks of feeding with highsalt vs. normal-salt chow. After 8 weeks on the CDAA diet, the degree of hepatic steatosis did not differ between the high-salt and normal-salt groups; however, alanine aminotransferase and fasting blood glucose levels were significantly higher and hepatic mRNA levels for interleukin (IL)-10 and heme oxygenase (HO)-1 were significantly lower in the high-salt group compared with the normal-salt group. After 24 weeks on the CDAA diet, the high-salt group had significantly more severe hepatic fibrosis and a higher hepatic mRNA expression of α-smooth muscle actin and lower hepatic IL-10 and HO-1 mRNA levels compared with the normal-salt group. In conclusion, our results indicate that hypertension is a potential risk factor for liver injury and hepatic fibrosis through glucose intolerance and decreased IL-10-mediated or HO-1-induced anti-inflammatory mechanisms. IntroductionNon-alcoholic fatty liver disease (NAFLD) includes nonalcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH), and NASH may lead to hepatic cirrhosis or hepatocellular carcinoma (HCC) (1,2). NAFLD/NASH can be viewed as a metabolic syndrome phenotype involving the liver, and the incidence of NAFLD has increased with corresponding increases in risk factors for metabolic syndrome, such as obesity, diabetes and hypertension. Such metabolic risk factors may promote the pathological progression of NAFLD/NASH, and NAFLD advances more rapidly in patients with a greater number of metabolic risk factors (3,4).The incidence of hypertension is significantly higher in patients with NAFLD compared with the general population (5). Furthermore, a higher incidence of NASH has been observed in patients with NAFLD who also have hypertension and these patients are likely to progress to advanced hepatic fibrosis (6), which suggests that hypertension may promote the onset or progression of hepatitis and hepatic fibrosis. However, the possible association between hypertension and the pathological progression of NAFLD has not been fully established.Rats fed a choline-deficient L-amino acid-defined (CDAA) diet initially develop fatty liver and hepatitis, and may subsequently progress to hepatic fibrosis and HCC (7). These findings indic...

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“…On the other hand, the SHR strain is the most widely used phenotypic experimental model in hypertension research with specific potential in the study of polygenic hypertension, being associated with cardiac hypertrophy, heart failure, and renal dysfunction. Hepatic functions are also altered at the molecular level in this model of primary hypertension[42]. …”

Section: Discussionmentioning

confidence: 99%

Angiotensin II or epinephrine hemodynamic and metabolic responses in the liver of L-NAME induced hypertension and spontaneous hypertensive rats

Kimura¹,

Nagaoka²,

Borges³

et al. 2017

WJH

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AIMTo study hepatic vasoconstriction and glucose release induced by angiotensin (Ang)II or Epi in rats with pharmacological hypertension and spontaneously hypertensive rat (SHR).METHODSIsolated liver perfusion was performed following portal vein and vena cava cannulation; AngII or epinephrine (Epi) was injected in bolus and portal pressure monitored; glucose release was measured in perfusate aliquots.RESULTSThe portal hypertensive response (PHR) and the glucose release induced by AngII of L-NAME were similar to normal rats (WIS). On the other hand, the PHR induced by Epi in L-NAME was higher whereas the glucose release was lower compared to WIS. Despite the similar glycogen content, glucose release induced by AngII was lower in SHR compared to Wistar-Kyoto rats although both PHR and glucose release induced by Epi in were similar.CONCLUSIONAngII and Epi responses are altered in different ways in these hypertension models. Our results suggest that inhibition of NO production seems to be involved in the hepatic effects induced by Epi but not by AngII; the diminished glucose release induced by AngII in SHR is not related to glycogen content.

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Changes in hepatic protein expression in spontaneously hypertensive rats suggest early stages of non-alcoholic fatty liver disease

Cited by 16 publications

References 77 publications

Increased Sensitivity of the Circadian System to Temporal Changes in the Feeding Regime of Spontaneously Hypertensive Rats - A Potential Role for Bmal2 in the Liver

Increased Sensitivity of the Circadian System to Temporal Changes in the Feeding Regime of Spontaneously Hypertensive Rats - A Potential Role for Bmal2 in the Liver

Hypertension exacerbates liver injury and hepatic fibrosis induced by a choline-deficient L-amino acid-defined diet in rats

Angiotensin II or epinephrine hemodynamic and metabolic responses in the liver of L-NAME induced hypertension and spontaneous hypertensive rats

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