- Research article
- Open Access
Change in mRNA expression of sirtuin 1 and sirtuin 3 in cats fed on high fat diet
© Ishikawa et al.; licensee BioMed Central Ltd. 2013
Received: 23 May 2013
Accepted: 23 September 2013
Published: 27 September 2013
Mammalian 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.
Cat 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).
Cat 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.
Mammalian sirtuins have been identified as homologs of the yeast silent information regulator 2 (Sir2) , which is an NAD-dependent deacetylase and related to metabolism and longevity in yeast . Seven mammalian sirtuins are included in the family and each has different target proteins. Sirtuin 1 (SIRT1) is found primarily in the nucleus  and plays important roles in maintaining metabolic functions and immune responses through deacetylation of many substrates, such as forkhead transcription factors , peroxisome proliferator-activated receptor-gamma, coactivator 1-alpha  and the p65 subunit of nuclear factor-kappa B (NF-κB) . SIRT3 is localized to mitochondria  and protects cells from oxidative stress-induced cell death by deacetylating isocitrate dehydrogenase 2  and superoxide dismutase 2 . Gene expression and activity of sirtuins are mainly regulated by metabolic states and aging . These features of SIRT1 and SIRT3 have been studied in metabolic diseases related to aging such as type 2 diabetes mellitus (DM) [11, 12], fatty liver [13, 14], and heart diseases [15, 16].
Prevalence of obesity has increased in cats, and obesity leads to the development of DM  and hepatic lipidosis . Because the clinical, physiological, and pathological features of DM in cats closely resemble those in humans, cats are good animal models for human type 2 DM . However, very little information is available on cat SIRT1 and SIRT3. The aims of this study were to determine the cDNA sequences, and examine the SIRT1 and SIRT3 mRNA expression in several tissues (Experiment 1), and to investigate the effects of feeding a high-fat diet (HFD) on the SIRT1 and SIRT3 expression (Experiment 2) in cats.
CDNA cloning of cat SIRT1 and SIRT3
Cat SIRT1 and SIRT3 mRNA expression profiles in tissues
Changes in cat SIRT1 and SIRT3 gene expression after HFD feeding
Clinical characteristics and plasma metabolite concentrations
Body weight (kg)
2.6 ± 0.2
3.2 ± 0.3**
Total cholesterol (mg/dL)
100.6 ± 4.3
100.6 ± 9.4
Alanine aminotransferase (U/L)
41.6 ± 4.7
69.6 ± 6.8**
Alkaline phosphatase (U/L)
76.6 ± 14.5
101.2 ± 12.2**
Aspartate aminotransferase (U/L)
24.8 ± 1.3
32.2 ± 1.1**
Lactate dehydrogenase (U/L)
141.8 ± 21.9
131.4 ± 19.9
Serum total protein (g/dL)
6.5 ± 0.2
6.7 ± 0.2
72.6 ± 3.1
77.3 ± 0.6
Blood urea nitrogen (mg/dL)
20.0 ± 1.5
21.4 ± 0.9
0.9 ± 0.2
1.0 ± 0.1
We successfully cloned the cat SIRT1 and SIRT3 cDNAs. Sequence alignment of the cat SIRT1 and SIRT3 amino acids revealed that they contained a conserved catalytic core domain . This core domain included the motifs CxxC-(18–20)x-CxxC, which are known to be involved in zinc fingers, and conserved in all Sir2-like enzymes . The other highly conserved motifs GAG(I/V)SxxxG(I/V)PDFRS, TQNID, and HG(S/T) create NAD+ binding sites . SIRT1 and SIRT3 were genetically conserved in the phylogenetic tree, and may have an enzymatic function in cats.
SIRT1 and SIRT3 mRNA are expressed in a variety of tissues in humans [1, 7], mice , cows,  and pigs . In our study, cat SIRT1 and SIRT3 mRNA was expressed in various tissues similar to other animals, and high expression levels were observed in the liver and skeletal muscle for SIRT1 and in the heart for SIRT3 in cats. In an SIRT1 heterozygous knockout mice study, acceleration of hepatic steatosis and increased inflammatory gene expressions were observed in the liver . Liver expression of cat SIRT1 may be related to control fatty acid homeostasis. Since SIRT1 enhance skeletal muscle insulin sensitivity in mice , a high SIRT1 mRNA expression levels in the skeletal muscle is considered to be related to glucose metabolism in cats. Although SIRT3 deficient mice appear to have normal activity, they show signs of cardiac hypertrophy at 8 weeks of age . Cat SIRT3 expression in the heart may be related to protection against cardiac hypertrophy. Hypertrophic cardiomyopathy (HCM) is the most common heart disease in cats and remains a major cause of morbidity and mortality associated with the risk of sudden death . Therefore, we think it might be interesting to study the relationship between SIRT3 and HCM in cats. Additionally, both SIRT1 and SIRT3 expression levels in the pancreas were different between individuals. SIRT1 regulate insulin secretion in pancreatic β cells  and SIRT3 is suppressed in pancreatic islets isolated from human type 2 diabetic patients . Therefore, the expression levels of SIRT1 and SIRT3 in the pancreas may be considered to be fluctuating by the metabolic state in cats.
Sirtuins are regulated by nutritional status, for instance, caloric restriction up-regulates SIRT1  and SIRT3  activity in cultured mammalian cells. In contrast, obesity and HFD reduce SIRT1  and SIRT3  activity in vivo. SIRT1 protein expression is down-regulated in the liver of rat and adipose tissue of mice [13, 33], whereas expression of cat SIRT1 mRNA was up-regulated in peripheral blood leukocytes by HFD. These differences in expression patterns may be considered to be differences in reactivity to HFD between tissues. In our study, early phase liver inflammation was inferred because hepatocellular injury markers were up-regulated by HFD. Some inflammatory factors are released in greater amounts from adipose tissue in obese subjects and cause chronic inflammation in animals [34, 35]. HFD triggers a pro-inflammatory effect, and induces SIRT1 cleavage in adipose tissue . On the other hand, pro-inflammatory factors enhance the NF-κB signal, and SIRT1 mRNA is also up-regulated as part of a feedback mechanism . In addition, SIRT1 inhibits inflammatory pathways in macrophages to regulate inflammatory responses . Hence we propose the hypothesis that HFD induces early phase inflammation in tissues such as liver and adipose tissue, and cat SIRT1 mRNA expression levels is up-regulated in peripheral blood leukocytes to suppress inflammation. Since peripheral blood leukocytes SIRT1 mRNA level was increase before total cholesterol and glucose level is increase, SIRT1 may become a candidate marker for early diagnosis of metabolic diseases including obesity in cats.
Our study reveals the full length cat SIRT1 and SIRT3 by cDNA cloning and found that these SIRTs were highly conserved among vertebrates. And the mRNA expression analysis 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 were different between individuals. Our results provide fundamental information to reveal the cat SIRT1 and SIRT3 function about relationship of metabolic diseases. Furthermore, HFD affected cat SIRT1 mRNA expression in peripheral blood leukocytes. This represent HFD feeding may be related to SIRT1 mRNA expression mechanisms in cat peripheral blood leukocytes.
Cloning of cat SIRT1 and SIRT3 cDNA
Sequences and kind of primers used for polymerase chain reaction
Quantitative real-time PCR (q-PCR) analysis of SIRT1 and SIRT3 in various cat tissues
Total RNA (1 μg) was reverse transcribed by QuantiTect Reverse Transcription Kit (Qiagen, Hilden, Germany). Genomic DNA was removed by DNase treatment, and cDNA was synthesized. After inactivating the reverse transcription reaction by heating at 95°C for 3 min, the cDNA product was used for q-PCR. Reactions were carried out with Perfect Real Time SYBR Premix Ex Taq II (Takara) using an ABI 7300 Real Time PCR Sequence Detection System (Applied Biosystems, Foster City, CA) and the following Shuttle PCR protocol: 95°C for 30 s, followed by 40 cycles of 95°C for 5 s, and 60°C for 35 s, in 20 μl reaction volumes containing 2 μl template cDNA, 0.8 μl primers (0.4 μl of each), 10 μl of SYBR Premix Ex Taq II, 0.4 μl ROX Reference Dye, and 6.0 μl distilled water. Primers 5 and 6 and 11 and 12 were designed from the cloned SIRT1 and SIRT3 sequences respectively. Primers 13 and 14 were used for beta-actin mRNA. Following the real-time PCR, the fragment was subjected to dissociation-curve analysis to avoid nonspecific PCR amplification. Quantitative measurements were performed by establishing a linear amplification curve from serial dilutions of the plasmid containing cat SIRT1, SIRT3, and beta-actin cDNA fragments.
This experiment was conducted with 5 domestic female cats (mean age, 14.0 ± 1.4 months; age range, 10–30 months; body weight [BW], 2.5 ± 0.1 kg). Veterinarians confirmed that the cats were healthy and without any clinical manifestations. All cats were individually housed and maintained for 6 weeks at AQS Co. Ltd. (Narita, Japan). The cats were fed on HFD, which was made to order by Nippon Pet Food, Inc. (Tokyo, Japan). The composition of HFD was moisture (7.0%), crude protein (32.7%), crude fat (23.9%), crude fiber (0.9%), crude ash (5.5%), and nitrogen free extract (29.9%). The caloric content was 4660 kcal/kg. The fatty acid composition of HFD was 14:0 (1.3%), 14:1 (0.4%), 15:0 (0.2%), 16:0 (22.6%), 16:1 (2.3%), 17:0 (0.4%), 17:1 (0.3%), 18:0 (23.1%), 18:1 (35.7%), 18:2n-6 (10.9%), 18:3n-3 (0.4%), 20:0 (0.5%), 20:1 (0.3%), 20:4n-6 (0.2%), 22:0 (0.2%), and unidentified (1.2%). The cats were fed the diet ad libitum for their daily energy requirement (DER) from 9:00 AM to 8:30 AM the next day. Any surplus diet was removed at 4:00 PM a day prior to blood sampling. DER was calculated as 1.4 × resting energy requirement (RER) (BW0.75 × 70). RER was based on BW before the meal at 9:00 AM. Cats were housed in individual cages and provided with water ad libitum. The animal room was maintained at 24 ± 2°C and 55 ± 10% relative humidity on a 12:12 h light: dark cycle (lights on from 8:00 AM to 8:00 PM). Approval for this study was provided by the Nippon Veterinary and Life Science University Animal Research Committee.
Pre-prandial blood samples (4–5 ml) were withdrawn from the jugular vein of cats without sedation prior to the 6 week feeding period (Baseline); 2.5 ml of this blood was collected in PAX gene RNA tubes (PreAnalytiX, Hombrechtikon, Switzerland) for RNA stabilization, preservation, and sample transport, and the remainder was collected in heparinized tubes, for immediate centrifugation at 1500 × g for 10 min at 4°C to obtain plasma, which was stored at -30°C until analysis. At the conclusion of the 6 week feeding schedule (Endpoint), pre-prandial blood (5 ml) was withdrawn again from the same site and treated in the same manner.
Plasma metabolite and hepatic injury marker enzyme analysis
Plasma total cholesterol, total protein, glucose, blood urea nitrogen, and creatinine concentrations as well as alanine aminotransferase (ALT), alkaline phosphatase (ALP), asparate aminotransferase (AST), and lactate dehydrogenase activities were determined using an autoanalyzer (AU680, Beckman Coulter, CA, USA).
q-PCR analysis of peripheral blood leukocyte mRNA
Total leukocyte RNA was extracted from the blood samples using TRIzol (Invitrogen), according to the manufacturer’s protocol. RNA concentration was assessed by spectrophotometer at 260 nm, and the presence of isolated RNA was assessed by native agarose gel electrophoresis on a 0.8% agarose gel. The cDNA synthesis and q-PCR analysis were performed as described above.
Data are presented as mean ± standard error of mean (SEM) and were analyzed using Student’s paired t-test. All analyses were performed using GraphPad Prism (GraphPad Software, San Diego, CA). A P < 0.05 was considered significant.
The authors would like to thank Enago (http://www.enago.jp) for the English language review.
- Frye RA: Characterization of five human cDNAs with homology to the yeast SIR2 gene: Sir2-like proteins (sirtuins) metabolize NAD and may have protein ADP-ribosyltransferase activity. Biochem Biophys Res Commun. 1999, 260 (1): 273-279. 10.1006/bbrc.1999.0897.PubMedView ArticleGoogle Scholar
- Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE, Chung P, Kisielewski A, Zhang LL, Scherer B, Sinclair DA: Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature. 2003, 425 (6954): 191-196. 10.1038/nature01960.PubMedView ArticleGoogle Scholar
- Michishita E, Park JY, Burneskis JM, Barrett JC, Horikawa I: Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins. Mol Biol Cell. 2005, 16 (10): 4623-4635. 10.1091/mbc.E05-01-0033.PubMedPubMed CentralView ArticleGoogle Scholar
- Brunet A, Sweeney LB, Sturgill JF, Chua KF, Greer PL, Lin Y, Tran H, Ross SE, Mostoslavsky R, Cohen HY, Hu LS, Cheng HL, Jedrychowski MP, Gygi SP, Sinclair DA, Alt FW, Greenberg ME: Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science. 2004, 303 (5666): 2011-2015. 10.1126/science.1094637.PubMedView ArticleGoogle Scholar
- Rodgers JT, Lerin C, Haas W, Gygi SP, Spiegelman BM, Puigserver P: Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1. Nature. 2005, 434 (7029): 113-118. 10.1038/nature03354.PubMedView ArticleGoogle Scholar
- Zhang HN, Li L, Gao P, Chen HZ, Zhang R, Wei YS, Liu DP, Liang CC: Involvement of the p65/RelA subunit of NF-kappaB in TNF-alpha-induced SIRT1 expression in vascular smooth muscle cells. Biochem Biophys Res Commun. 2010, 397 (3): 569-575. 10.1016/j.bbrc.2010.05.160.PubMedView ArticleGoogle Scholar
- Onyango P, Celic I, McCaffery JM, Boeke JD, Feinberg AP: SIRT3, A human SIR2 homologue, is an NAD-dependent deacetylase localized to mitochondria. Proc Natl Acad Sci U S A. 2002, 99 (21): 13653-13658. 10.1073/pnas.222538099.PubMedPubMed CentralView ArticleGoogle Scholar
- Someya S, Yu W, Hallows WC, Xu J, Vann JM, Leeuwenburgh C, Tanokura M, Denu JM, Prolla TA: Sirt3 Mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restriction. Cell. 2010, 143 (5): 802-812. 10.1016/j.cell.2010.10.002.PubMedPubMed CentralView ArticleGoogle Scholar
- Qiu X, Brown K, Hirschey MD, Verdin E, Chen D: Calorie restriction reduces oxidative stress by SIRT3-mediated SOD2 activation. Cell Metab. 2010, 12 (6): 662-667. 10.1016/j.cmet.2010.11.015.PubMedView ArticleGoogle Scholar
- Longo VD, Kennedy BK: Sirtuins in aging and age-related disease. Cell. 2006, 126 (2): 257-268. 10.1016/j.cell.2006.07.002.PubMedView ArticleGoogle Scholar
- Banks AS, Kon N, Knight C, Matsumoto M, Gutiérrez-Juárez R, Rossetti L, Gu W, Accili D: SirT1 Gain of function increases energy efficiency and prevents diabetes in mice. Cell Metab. 2008, 8 (4): 333-341. 10.1016/j.cmet.2008.08.014.PubMedPubMed CentralView ArticleGoogle Scholar
- Jing E, Emanuelli B, Hirschey MD, Boucher J, Lee KY, Lombard D, Verdin EM, Kahn CR: Sirtuin-3 (Sirt3) regulates skeletal muscle metabolism and insulin signaling via altered mitochondrial oxidation and reactive oxygen species production. Proc Natl Acad Sci U S A. 2011, 108 (35): 14608-14613. 10.1073/pnas.1111308108.PubMedPubMed CentralView ArticleGoogle Scholar
- Deng XQ, Chen LL, Li NX: The expression of SIRT1 in nonalcoholic fatty liver disease induced by high-fat diet in rats. Liver Int. 2007, 27 (5): 708-715. 10.1111/j.1478-3231.2007.01497.x.PubMedView ArticleGoogle Scholar
- Kendrick AA, Choudhury M, Rahman SM, McCurdy CE, Friederich M, Van Hove JL, Watson PA, Birdsey N, Bao J, Gius D, Sack MN, Jing E, Kahn CR, Friedman JE, Jonscher KR: Fatty liver is associated with reduced SIRT3 activity and mitochondrial protein hyperacetylation. Biochem J. 2011, 433 (3): 505-514. 10.1042/BJ20100791.PubMedPubMed CentralView ArticleGoogle Scholar
- Tanno M, Kuno A, Yano T, Miura T, Hisahara S, Ishikawa S, Shimamoto K, Horio Y: Induction of manganese superoxide dismutase by nuclear translocation and activation of SIRT1 promotes cell survival in chronic heart failure. J Biol Chem. 2010, 285 (11): 8375-8382. 10.1074/jbc.M109.090266.PubMedPubMed CentralView ArticleGoogle Scholar
- Pillai VB, Sundaresan NR, Kim G, Gupta M, Rajamohan SB, Pillai JB, Samant S, Ravindra PV, Isbatan A, Gupta MP: Exogenous NAD blocks cardiac hypertrophic response via activation of the SIRT3-LKB1-AMP-activated kinase pathway. J Biol Chem. 2010, 285 (5): 3133-3144. 10.1074/jbc.M109.077271.PubMedPubMed CentralView ArticleGoogle Scholar
- O’Brien TD: Pathogenesis of feline diabetes mellitus. Mol Cell Endocrinol. 2002, 197 (1–2): 213-219.PubMedView ArticleGoogle Scholar
- Armstrong PJ, Blanchard G: Hepatic lipidosis in cats. Vet Clin North Am Small Anim Pract. 2009, 39 (3): 599-616. 10.1016/j.cvsm.2009.03.003.PubMedView ArticleGoogle Scholar
- Henson MS, O’Brien TD: Feline models of type 2 diabetes mellitus. ILAR J. 2006, 47 (3): 234-242. 10.1093/ilar.47.3.234.PubMedView ArticleGoogle Scholar
- Sanders BD, Jackson B, Marmorstein R: Structural basis for sirtuin function: what we know and what we don’t. Biochim Biophys Acta. 2010, 1804 (8): 1604-1616. 10.1016/j.bbapap.2009.09.009.PubMedPubMed CentralView ArticleGoogle Scholar
- Sherman JM, Stone EM, Freeman-Cook LL, Brachmann CB, Boeke JD, Pillus L: The conserved core of a human SIR2 homologue functions in yeast silencing. Mol Biol Cell. 1999, 10 (9): 3045-3059. 10.1091/mbc.10.9.3045.PubMedPubMed CentralView ArticleGoogle Scholar
- Min J, Landry J, Sternglanz R, Xu RM: Crystal structure of a SIR2 homolog-NAD complex. Cell. 2001, 105 (2): 269-279. 10.1016/S0092-8674(01)00317-8.PubMedView ArticleGoogle Scholar
- Shi T, Wang F, Stieren E, Tong Q: SIRT3, A mitochondrial sirtuin deacetylase, regulates mitochondrial function and thermogenesis in brown adipocytes. J Biol Chem. 2005, 280 (14): 13560-13567. 10.1074/jbc.M414670200.PubMedView ArticleGoogle Scholar
- Ghinis-Hozumi Y, González-Gallardo A, González-Dávalos L, Antaramian A, Villarroya F, Shimada A, Varela-Echavarría A, Mora O: Bovine sirtuins: initial characterization and expression of sirtuins 1 and 3 in liver, muscle, and adipose tissue. J Anim Sci. 2011, 89 (8): 2529-2536. 10.2527/jas.2010-3476.PubMedView ArticleGoogle Scholar
- Jin D, Tan HJ, Lei T, Gan L, Chen XD, Long QQ, Feng B, Yang ZQ: Molecular cloning and characterization of porcine sirtuin genes. Comp Biochem Physiol B Biochem Mol Biol. 2009, 153 (4): 348-358. 10.1016/j.cbpb.2009.04.004.PubMedView ArticleGoogle Scholar
- Xu F, Gao Z, Zhang J, Rivera CA, Yin J, Weng J, Ye J: Lack of SIRT1 (mammalian sirtuin 1) activity leads to liver steatosis in the SIRT1+/- mice: a role of lipid mobilization and inflammation. Endocrinology. 2010, 151 (6): 2504-2514. 10.1210/en.2009-1013.PubMedPubMed CentralView ArticleGoogle Scholar
- Schenk S, McCurdy CE, Philp A, Chen MZ, Holliday MJ, Bandyopadhyay GK, Osborn O, Baar K, Olefsky JM: Sirt1 Enhances skeletal muscle insulin sensitivity in mice during caloric restriction. J Clin Invest. 2011, 121 (11): 4281-4288. 10.1172/JCI58554.PubMedPubMed CentralView ArticleGoogle Scholar
- Sundaresan NR, Gupta M, Kim G, Rajamohan SB, Isbatan A, Gupta MP: Sirt3 Blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice. J Clin Invest. 2009, 119 (9): 2758-2771.PubMedPubMed CentralGoogle Scholar
- Abbott JA: Feline hypertrophic cardiomyopathy: an update. Vet Clin North Am Small Anim Pract. 2010, 40 (4): 685-700. 10.1016/j.cvsm.2010.04.004.PubMedView ArticleGoogle Scholar
- Bordone L, Motta MC, Picard F, Robinson A, Jhala US, Apfeld J, McDonagh T, Lemieux M, McBurney M, Szilvasi A, Easlon EJ, Lin SJ, Guarente L: Sirt1 Regulates insulin secretion by repressing UCP2 in pancreatic beta cells. PLoS Biol. 2006, 4 (2): e31-10.1371/journal.pbio.0040031.PubMedPubMed CentralView ArticleGoogle Scholar
- Caton PW, Richardson SJ, Kieswich J, Bugliani M, Holland ML, Marchetti P, Morgan NG, Yaqoob MM, Holness MJ, Sugden MC: Sirtuin 3 regulates mouse pancreatic beta cell function and is suppressed in pancreatic islets isolated from human type 2 diabetic patients. Diabetologia. 2013, 56 (5): 1068-1077. 10.1007/s00125-013-2851-y.PubMedView ArticleGoogle Scholar
- Cohen HY, Miller C, Bitterman KJ, Wall NR, Hekking B, Kessler B, Howitz KT, Gorospe M, de Cabo R, Sinclair DA: Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science. 2004, 305 (5682): 390-392. 10.1126/science.1099196.PubMedView ArticleGoogle Scholar
- Chalkiadaki A, Guarente L: High-fat diet triggers inflammation-induced cleavage of SIRT1 in adipose tissue to promote metabolic dysfunction. Cell Metab. 2012, 16 (2): 180-188. 10.1016/j.cmet.2012.07.003.PubMedPubMed CentralView ArticleGoogle Scholar
- Hotamisligil GS: Inflammation and metabolic disorders. Nature. 2006, 444 (7121): 860-867. 10.1038/nature05485.PubMedView ArticleGoogle Scholar
- Laflamme DP: Companion animals symposium: obesity in dogs and cats: what is wrong with being fat?. J Anim Sci. 2012, 90 (5): 1653-1662. 10.2527/jas.2011-4571.PubMedView ArticleGoogle Scholar
- Yoshizaki T, Schenk S, Imamura T, Babendure JL, Sonoda N, Bae EJ, Oh DY, Lu M, Milne JC, Westphal C, Bandyopadhyay G, Olefsky JM: SIRT1 Inhibits inflammatory pathways in macrophages and modulates insulin sensitivity. Am J Physiol Endocrinol Metab. 2010, 298 (3): E419-E428. 10.1152/ajpendo.00417.2009.PubMedPubMed CentralView ArticleGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.