General Information:

Id: 904
Diseases: Diabetes mellitus, type II - [OMIM]
Fatty liver disease, nonalcoholic
Insulin resistance
Mus musculus
BAC-based transgenic Sirt1 mouse with moderate overexpression of Sirt1
article
Reference: Pfluger PT et al.(2008) Sirt1 protects against high-fat diet-induced metabolic damage Proc. Natl. Acad. Sci. U.S.A. 105: 9793-9798 [PMID: 18599449]

Interaction Information:

Comment Body weights and body lengths of 8- to 10-week-old transgenic Sirt1 mice did not differ from wild-type (WT) control mice on a standard diet (SD). Subsequent exposure for 19 weeks to a high-fat diet (HFD) did not lead to significant differences in body weight, fat mass, or lean mass, although a trend toward lower body weight and fat mass was observed in transgenic mice on HFD compared with WT controls.
Formal Description
Interaction-ID: 5370

gene/protein

SIRT1

NOT affects_activity of

if SIRT1 is overexpressed
Comment Neither plasma leptin levels nor adiponectin levels differed between genotypes on either SD or HFD.
Formal Description
Interaction-ID: 5373

gene/protein

SIRT1

NOT affects_quantity of

gene/protein

LEP

in blood; on standard diet, on high-fat diet, if SIRT1 is overexpressed
Comment Neither plasma leptin levels nor adiponectin levels differed between genotypes on either SD or HFD.
Formal Description
Interaction-ID: 5374

gene/protein

SIRT1

NOT affects_quantity of

gene/protein

ADIPOQ

in blood; on standard diet, on high-fat diet, if SIRT1 is overexpressed
Comment Transgenic Sirt1 mice exhibited increased food intake compared with wild-type mice on high-fat diet.
Formal Description
Interaction-ID: 5375

gene/protein

SIRT1

affects_activity of

on high-fat diet, if SIRT1 is overexpressed
Comment Indirect calorimetry revealed that transgenic Sirt1 mice showed higher energy expenditure than wild-type mice on high-fat diet. No differences were observed in mice fed standard diet.
Formal Description
Interaction-ID: 5376

gene/protein

SIRT1

affects_activity of

on high-fat diet, if SIRT1 is overexpressed
Comment Although Sirt1 transgenic mice present a modest increase in food intake under high-fat diet, this is compensated by a similarly modest increase in energy expenditure, thus indicating a balanced energy homeostasis.
Formal Description
Interaction-ID: 5379

gene/protein

SIRT1

NOT affects_activity of

on high-fat diet, if SIRT1 is overexpressed
Comment After 19 weeks of high-fat diet, wild-type mice presented with severe hepatosteatosis, including massive accumulation of large lipid droplets. Importantly, Sirt1 transgenic mice were almost entirely protected from NAFLD, showing a low number of lipid droplets with small diameters.
Formal Description
Interaction-ID: 5381

gene/protein

SIRT1

affects_activity of

disease

Fatty liver disease, nonalcoholic

after 19 weeks of high-fat diet, if SIRT1 is overexpressed
Comment In agreement with the observed Sirt1-mediated protection from hepatosteatosis, the authors found that Sirt1 transgenic mice presented lower levels of SREBP1c mRNA in response to high-fat diet.
Formal Description
Interaction-ID: 5382

gene/protein

SIRT1

affects_expression of

mRNA/protein variant

SREBF1c

in response to high-fat diet, if SIRT1 is overexpressed
Comment Sirt1 protects from NAFLD.
Formal Description
Interaction-ID: 5383

gene/protein

SIRT1

decreases_activity of

disease

Fatty liver disease, nonalcoholic

Comment Exposure to a high-fat diet and diet-induced obesity lead to a chronic inflammatory reaction, which is believed to be critical for the development of glucose intolerance and insulin resistance. The expression of IL-6 and TNF-alpha, two major proinflammatory cytokines, was significantly enhanced in livers of wild-type mice on a chronic high-fat diet (HFD). Transgenic mice on HFD, however, still exhibited low levels of inflammatory markers, comparable to those seen in wild-type and transgenic mice on chow diet.
Formal Description
Interaction-ID: 5384

environment

high-fat diet

increases_expression of

gene/protein

IL6

in liver
Drugbank entries Show/Hide entries for IL6
Comment Exposure to a high-fat diet and diet-induced obesity lead to a chronic inflammatory reaction, which is believed to be critical for the development of glucose intolerance and insulin resistance. The expression of IL-6 and TNF-alpha, two major proinflammatory cytokines, was significantly enhanced in livers of wild-type mice on a chronic high-fat diet (HFD). Transgenic mice on HFD, however, still exhibited low levels of inflammatory markers, comparable to those seen in wild-type and transgenic mice on chow diet.
Formal Description
Interaction-ID: 5387

environment

high-fat diet

increases_expression of

gene/protein

TNF

in liver
Drugbank entries Show/Hide entries for TNF
Comment Exposure to a high-fat diet and diet-induced obesity lead to a chronic inflammatory reaction, which is believed to be critical for the development of glucose intolerance and insulin resistance. The expression of IL-6 and TNF-alpha, two major proinflammatory cytokines, was significantly enhanced in livers of wild-type mice on a chronic high-fat diet (HFD). Transgenic mice on HFD, however, still exhibited low levels of inflammatory markers, comparable to those seen in wild-type and transgenic mice on chow diet.
Formal Description
Interaction-ID: 5388

gene/protein

SIRT1

NOT affects_expression of

gene/protein

IL6

in liver; in response to high-fat diet, if SIRT1 is overexpressed
Drugbank entries Show/Hide entries for IL6
Comment Exposure to a high-fat diet and diet-induced obesity lead to a chronic inflammatory reaction, which is believed to be critical for the development of glucose intolerance and insulin resistance. The expression of IL-6 and TNF-alpha, two major proinflammatory cytokines, was significantly enhanced in livers of wild-type mice on a chronic high-fat diet (HFD). Transgenic mice on HFD, however, still exhibited low levels of inflammatory markers, comparable to those seen in wild-type and transgenic mice on chow diet.
Formal Description
Interaction-ID: 5389

gene/protein

SIRT1

NOT affects_expression of

gene/protein

TNF

in liver; in response to high-fat diet, if SIRT1 is overexpressed
Drugbank entries Show/Hide entries for TNF
Comment TNF-alpha stimulation resulted in significantly lower activation of NF-kappaB activation in Sirt1-transgenic cells (2.8-fold) compared with wild-type cells (5-fold).
Formal Description
Interaction-ID: 5394

gene/protein

SIRT1

affects_activity of

complex/PPI

NF-kappaB complex

if SIRT1 is overexpressed
Comment In addition to the reduced expression of inflammatory cytokines, the expression of the antioxidant proteins manganese superoxide dismutase (MnSOD) and the nuclear respiratory factor 1 (Nrf1), a master regulator in the protection from reactive oxygen species, were both increased in transgenic mice on both standard diet and high-fat diet, compared with wild-type mice. Both genes, MnSOD and Nrf1, have been demonstrated to be induced by PGC1alpha, which in turn is positively regulated by Sirt1.
Formal Description
Interaction-ID: 5396

gene/protein

SIRT1

affects_expression of

gene/protein

SOD2

on standard diet, on high-fat diet, if SIRT1 is overexpressed
Drugbank entries Show/Hide entries for SOD2
Comment The overexpression of Sirt1 appears to protect transgenic mice from high-fat diet-induced hepatic inflammation through decreasing the NF-kappaB-mediated induction of inflammatory cytokines, as well as by the activation of antioxidant proteins, possibly mediated by PGC1alpha.
Formal Description
Interaction-ID: 5399

gene/protein

SIRT1

decreases_activity of

if SIRT1 is overexpressed, via decreased NF-kappaB activity
Comment Indirect calorimetry revealed that transgenic Sirt1 mice showed higher energy expenditure than wild-type mice on high-fat diet. No differences were observed in mice fed standard diet.
Formal Description
Interaction-ID: 13187

gene/protein

SIRT1

NOT affects_activity of

on standard diet, if SIRT1 is overexpressed
Comment In addition to the reduced expression of inflammatory cytokines, the expression of the antioxidant proteins manganese superoxide dismutase (MnSOD) and the nuclear respiratory factor 1 (Nrf1), a master regulator in the protection from reactive oxygen species, were both increased in transgenic mice on both standard diet and high-fat diet, compared with wild-type mice. Both genes, MnSOD and Nrf1, have been demonstrated to be induced by PGC1alpha, which in turn is positively regulated by Sirt1.
Formal Description
Interaction-ID: 13191

gene/protein

SIRT1

affects_expression of

gene/protein

NRF1

on standard diet, on high-fat diet, if SIRT1 is overexpressed
Comment In addition to the reduced expression of inflammatory cytokines, the expression of the antioxidant proteins manganese superoxide dismutase (MnSOD) and the nuclear respiratory factor 1 (Nrf1), a master regulator in the protection from reactive oxygen species, were both increased in transgenic mice on both standard diet and high-fat diet, compared with wild-type mice. Both genes, MnSOD and Nrf1, have been demonstrated to be induced by PGC1alpha, which in turn is positively regulated by Sirt1.
Formal Description
Interaction-ID: 13192

gene/protein

SIRT1

increases_activity of

gene/protein

PPARGC1A

on standard diet, on high-fat diet, if SIRT1 is overexpressed
Comment The overexpression of Sirt1 appears to protect transgenic mice from high-fat diet-induced hepatic inflammation through decreasing the NF-kappaB-mediated induction of inflammatory cytokines, as well as by the activation of antioxidant proteins, possibly mediated by PGC1alpha.
Formal Description
Interaction-ID: 13193

gene/protein

SIRT1

decreases_activity of

if SIRT1 is overexpressed