Change in mRNA expression of sirtuin 1 and sirtuin 3 in cats fed on high fat diet

Abstract

BackgroundMammalian sirtuins are homologs to the yeast silent information regulator 2 (Sir2), which is an NAD-dependent deacetylase. Sirtuins are comprised of 7 proteins, and each has different target proteins. Sirtuin 1 (SIRT1) plays important roles in maintaining metabolic functions and immune responses, and SIRT3 protects cells from oxidative stress-induced cell death. Both SIRT1 and SIRT3 are regulated by metabolic status and aging. Hence, SIRT1 and SIRT3 have been researched in metabolic diseases, such as type 2 diabetes mellitus (DM), fatty liver, and heart diseases. Although these diseases have been increasing, there is little information about relation between the diseases and SIRT1 and SIRT3 in cats. Therefore we cloned SIRT1 and SIRT3 cDNA, examined mRNA expression in cat tissues, and investigated the changes in SIRT1 and SIRT3 mRNA expression in peripheral blood leukocyte of cats fed on HFD for 6 weeks.ResultsCat SIRT1 and SIRT3 contained a catalytic core region and showed high sequence homology with other vertebrate SIRT1 (>61.3%) and SIRT3 (>65.9%) amino acids. Real-time polymerase chain reaction analyses revealed that high expression levels were observed in the liver and skeletal muscle for SIRT1 and in the heart for SIRT3 in cats. In addition, both cat SIRT1 and SIRT3 expression levels in the pancreas were different between individuals. Cat SIRT1 mRNA expression in peripheral blood leukocytes was significantly elevated in obese cats fed on HFD (P < 0.05).ConclusionsCat SIRT1 and SIRT3 genes are highly conserved among vertebrates, and HFD feeding may be related to SIRT1 mRNA expression mechanisms in cat peripheral blood leukocytes.

Tissue-specific regulation of sirtuin and nicotinamide adenine dinucleotide biosynthetic pathways identified in C57Bl/6 mice in response to high-fat feeding

“…Sirtuins are activated in response to metabolic stressors such HFD, while NAD biosynthesis is compromised at the same time [5,10,11]. This implies the potential for the system to become overwhelmed in response to chronic challenges.…”

Nicotinamide and NAFLD: Is There Nothing New Under the Sun?

“…NAD is synthesized with circadian oscillations, leading to a circadian schedule of SIRT activation and mitochondrial metabolism, such as the oxidation of fatty acids [38]. SIRTs’ activity is dependent on its cofactor NAD and it is sensitive to the cellular NAD levels [39], designating NAD as a rate-limiting substrate for their reactions [32,40,41]. As NAM is the product of SIRT-catalyzed deacetylation reactions, high levels of NAM have been used as a SIRTs inhibitor [42].…”

Sirtuins, aging, and cardiovascular risks

“…However, they exhibit cardiac hypertrophy at 8 weeks of age, expressed cardiac stress markers, had significantly higher heart/body weights ratio and interstitial fibrosis, and the ability to withstand oxidative stress is significantly reduced compared with wild-type mice (Hafner et al 2010;Sundaresan et al 2009;Wang et al 2014, Loffredo et al 2014. Moreover, cardiomyocytes cultured from SIRT3-deficient hearts produced higher levels of oxidative stress than did myocytes cultured from wild-type hearts (Ishikawa et al 2013;Sundaresan et al 2009). Overexpression of SIRT3 blunts cardiac hypertrophy by decreasing oxidative stress via upregulation of endogenous antioxidants (like Mn-SOD2 and catalase).…”