Lower cardiovagal tone and baroreflex sensitivity associated with hepatic insulin resistance and promote cardiovascular disorders in Tibetan minipigs induced by a high fat and high cholesterol diet.
AIMS
A long-term high-fat/cholesterol (HFC) diet leads to hepatic insulin resistance (IR), which is associated with autonomic dysfunction and cardiovascular diseases risk increasing. However, whether this occurs in Tibetan minipigs remains unknown. We tested that a long-term HFC diet caused hepatic IR and promote cardiovascular disorders in Tibetan minipigs, and are associated with the reduction of cardiovagal tone and baroreflex sensitivity (BRS).


METHODS
Male Tibetan minipigs were fed either a standard diet or a HFC diet, and were euthanized at 12 weeks. Thereafter, the minipigs were tested for biochemical blood indices, glucose tolerance, blood pressure, heart rate variability (HRV), BRS, and insulin receptor substrate (IRS)-associated gene and protein expression levels, as well as cardiac function.


RESULTS
HFC-fed minipigs developed IR by increasing body weight, total cholesterol, fasting blood glucose and insulin levels, and nonesterified fatty acid (NEFA) and high sensitive C-reactive protein (hs-CRP) levels, glucose intolerance. Increased adipose cell size, hepatic fat deposition, malondialdehyde (MDA) content and NEFA level, down-regulation of IRS1, IRS2, PI3K, Akt, p-Akt, Glut2 and PGC1ɑ expression concomitant with up-regulation of mTOR, GSK3β, TNF-ɑ, FOXO1, p-mTOR and p-p70S6K expression in the liver tissue, as well as hypertension and left ventricular diastolic dysfunction were observed in HFC-fed minipigs. HRV parameters and BRS values were further significantly reduced. Furthermore, multiple linear regression analysis showed that the development of hepatic IR toward cardiovascular disease was associated with low HFnu, RMSSD, BRS and LV -dp/dtmax, high NEFA, high hepatic TG content.


CONCLUSION
These data suggest that HFC-fed Tibetan minipigs develop hepatic IR and promote cardiovascular disorders, and are associated with lower cardiovagal tone and BRS.
['Pan|Yongming|Y|', 'Rong|Yili|Y|', 'Huang|Junjie|J|', 'Zhu|Keyan|K|', 'Chen|Jiaojiao|J|', 'Yu|Chen|C|', 'Chen|Minli|M|']
D000818:Animals D017704:Baroreflex D002318:Cardiovascular Diseases D002791:Cholesterol, Dietary D059305:Diet, High-Fat D004041:Dietary Fats D006321:Heart D007333:Insulin Resistance D008099:Liver D008297:Male D013552:Swine D013556:Swine, Miniature D014630:Vagus Nerve
Cardiovagal tone Baroreflex sensitivity Hepatic insulin resistance Tibetan minipig Hepatic steatosis High-fat/cholesterol diet