The role of hepatic SIRT1 on metabolic regulation under different energy status
Date Issued
2012
Date
2012
Author(s)
Liu, Chia-Hsin
Abstract
Sirtuin 1, also called SIRT1, is one member of sirtuin family proteins in mammals. SIRT1 and its invertebrate homologue, silencing information regulator 2 (Sir2), both are nicotinamide adenine dinucleotide (NAD+) -dependent enzymes that exert deacetylating action on acetyl-Lysine of proteins. Previous studies showed that SIRT1 and Sir2 were up-regulated under low energy conditions or calorie restriction (CR). Furthermore, increasing SIRT1 expression regulated its target proteins to modulate metabolic, neuronal and immunological functions, and therefore lead to anti-aging and longevity. This study was focused on the link between metabolic energy (ME) level and related gene expressions SIRT1 in various tissues of swine, and in mouse models in response to high fat diet (HFD).
In the first part of this study, 10-week-old Lanyu miniature pigs were fed with diet with various ME levels (2500 (L), 2700 (M) or 2900 (H) kcal/kg) for 10 weeks. There was no difference on body weight, feed conversion ratio and average daily gain among three groups. L group had a higher plasma level of triglyceride (TG), high density high density lipoprotein (HDL) and glucose than H group. Increased mRNA expression of SIRT1 and lipogenic genes were found in liver of L group. And hepatic triglyceride content was no different among three groups. These results suggested that low energy diet induced high efficiency by SIRT1, and fluxed to peripheral tissues for further use. In the second part of this study, 5-month-old Lanyu miniature pigs were fed with control (CON) or HFD, as 2700 or 3700 (HFD) kcal ME/kg, for 6-month period. HFD pigs had a higher body weight and backfat thickness, but no difference in blood parameters, including TG, total cholesterol, HDL and LDL level between two groups was observed. After 6 month experiment period, Lanyu pig was not induced obesity. HFD pigs had an increase in hepatic transcript and protein levels of SIRT1 and lipolytic genes, suggesting a protective role of SIRT1 in HFD-induced metabolic damage of porcine model.
In order to elucidate whether SIRT1 protects mice from HFD-induced metabolic damages in early stage of obesity, the third experiment was designed using 7-week-old mice as an animal model in response to high fat diet (HFD) for various duration. Results showed that SIRT1 mRNA expression increased with advancing age. Compared with CON mice, HFD mice had higher hepatic SIRT1 mRNA expression at 2-week period, while there was no difference after 25-week feeding. In addition, body weight, plasma TG, total cholesterol and glucose level were elevated since 2 week by HFD. These results suggested that SIRT1 might play a protective role in early obesity stage, and its activity and protection decline with advancing age.
Taken together, this study indicated that porcine hepatic SIRT1 expression was induced in CR as well as the rodent model. While in the high energy status induced by HFD-feeding 2 weeks, the hepatic SIRT1 expression of mice was elevated as well. These results suggest a protective role of SIRT1 in early obesity stage. However, the related mechanism needs further elucidation.
Subjects
calorie restriction
high fat diet
energy metabolism
Lanyu pig
mice
SDGs
Type
thesis
File(s)![Thumbnail Image]()
Loading...
Name
index.html
Size
23.49 KB
Format
HTML
Checksum
(MD5):d3be70c12fbe6b98c51a7edf00261c78