General Information:

Id: 1,347
Diseases: Diabetes mellitus, type II - [OMIM]
Fatty liver disease, nonalcoholic
Insulin resistance
Obesity - [OMIM]
Mus musculus
male
article
Reference: Ouchi N et al.(2010) Sfrp5 is an anti-inflammatory adipokine that modulates metabolic dysfunction in obesity. Science 329: 454-457 [PMID: 20558665]

Interaction Information:

Comment The secreted frizzled-related protein 5 (Sfrp5) was expressed at substantially higher levels in white adipose tissue than in other tissues at both the transcript and protein levels and the Sfrp5 transcript was confined to adipocytes rather than stromal vascular cells.
Formal Description
Interaction-ID: 9186

gene/protein

SFRP5

is_expressed_in

tissue/cell line

white adipose tissue

Comment Sfrp5 expression was reduced in obese leptin-deficient (ob/ob) mice.
Formal Description
Interaction-ID: 9190

organism model

ob/ob mouse

decreases_expression of

gene/protein

SFRP5

Comment Sfrp5 expression was also reduced in wild-type (WT) mice fed a HF-HS (high fat - high sucrose) diet for 24 weeks, but Sfrp5 expression was transiently upregulated after 12 weeks of the diet, when metabolic dysfunction and adipose tissue expression of markers of inflammation, macrophage infiltration, and oxidative and endoplasmic reticulum stresses are less severe.
Formal Description
Interaction-ID: 9191

environment

high-fat high-sucrose diet

decreases_expression of

gene/protein

SFRP5

after 24 weeks of diet
Comment Obesity led to higher levels of Wnt5a expression in adipose tissue and an increase in the ratio of Wnt5a to Sfrp5.
Formal Description
Interaction-ID: 9192

disease

Obesity

increases_expression of

gene/protein

SFRP5

in adipose tissue
Comment Although Sfrp5-/- mice fed a high fat high sucrose (HF-HS) diet showed a small, but significant, increase in body weight compared with WT mice, both strains had similar daily food intake during the experimental period of HF-HS diet feeding. Fasting glucose and insulin levels were elevated, and a greater degree of hepatic steatosis, with a higher triglyceride content and heavier liver weight, were observed in Sfrp5-/- mice compared with WT mice fed the HF-HS diet.
Formal Description
Interaction-ID: 9193

gene/protein

SFRP5

affects_activity of

disease

Fatty liver disease, nonalcoholic

after high-fat high-sucrose diet
Comment Transcript levels of F4/80 and CD68, both macrophage markers, were significantly elevated in epididymal adipose tissue of Sfrp5-/- mice compared with WT mice fed a high fat high sucrose diet, but not when given normal feed.
Formal Description
Interaction-ID: 9194

gene/protein

SFRP5

affects_expression of

gene/protein

ADGRE1

in epididymal adipose tissue; after high-fat high-sucrose diet
Comment Transcript levels of F4/80 and CD68, both macrophage markers, were significantly elevated in epididymal adipose tissue of Sfrp5-/- mice compared with WT mice fed a high fat high sucrose diet, but not when given normal feed.
Formal Description
Interaction-ID: 9195

gene/protein

SFRP5

affects_expression of

gene/protein

CD68

in epididymal adipose tissue; after high-fat high-sucrose diet
Comment When mice were fed a high fat high sucrose diet, significant increases in levels of TNFalpha, IL-6, and monocyte chemotactic protein-1 (MCP-1) transcripts occurred in the stromal vascular fraction from fat tissue of Sfrp5-/- mice compared with WT mice. Transcript levels of TNFalpha, IL-6, and MCP-1 did not differ between Sfrp5-/- and WT mice when given normal feed.
Formal Description
Interaction-ID: 9196

gene/protein

SFRP5

affects_expression of

gene/protein

TNF

in adipose tissue; after high-fat high-sucrose diet
Drugbank entries Show/Hide entries for TNF
Comment When mice were fed a high fat high sucrose diet, significant increases in levels of TNFalpha, IL-6, and monocyte chemotactic protein-1 (MCP-1) transcripts occurred in the stromal vascular fraction from fat tissue of Sfrp5-/- mice compared with WT mice. Transcript levels of TNFalpha, IL-6, and MCP-1 did not differ between Sfrp5-/- and WT mice when given normal feed.
Formal Description
Interaction-ID: 9197

gene/protein

SFRP5

affects_expression of

gene/protein

IL6

in adipose tissue; after high-fat high-sucrose diet
Drugbank entries Show/Hide entries for IL6
Comment When mice were fed a high fat high sucrose diet, significant increases in levels of TNFalpha, IL-6, and monocyte chemotactic protein-1 (MCP-1) transcripts occurred in the stromal vascular fraction from fat tissue of Sfrp5-/- mice compared with WT mice. Transcript levels of TNFalpha, IL-6, and MCP-1 did not differ between Sfrp5-/- and WT mice when given normal feed.
Formal Description
Interaction-ID: 9198

gene/protein

SFRP5

affects_expression of

gene/protein

CCL2

in adipose tissue; after high-fat high-sucrose diet
Drugbank entries Show/Hide entries for CCL2
Comment To analyze the downstream signaling pathways affected by Sfrp5 deficiency, the authors assessed whether the canonical or noncanonical Wnt signaling pathways were activated in epididymal adipose tissues of Sfrp5-/- and WT mice fed a high fat high sucrose diet. No differences were detected in transcript expression of cyclin D1 or WISP-2, indicators of canonical Wnt signaling, between Sfrp5-/- and WT mice. In contrast, phosphorylation of c-Jun N-terminal kinase (JNK), a downstream target of the noncanonical Wnt signaling, was elevated in white adipose tissue in Sfrp5-/- mice. Also, the phosphorylation of c-Jun, a downstream substrate of JNK, was elevated in Sfrp5-/- mice compared with WT mice.
Formal Description
Interaction-ID: 9199

gene/protein

SFRP5

NOT affects_expression of

gene/protein

CCND1

in epididymal adipose tissues; after high-fat high-sucrose diet
Drugbank entries Show/Hide entries for CCND1
Comment To analyze the downstream signaling pathways affected by Sfrp5 deficiency, the authors assessed whether the canonical or noncanonical Wnt signaling pathways were activated in epididymal adipose tissues of Sfrp5-/- and WT mice fed a high fat high sucrose diet. No differences were detected in transcript expression of cyclin D1 or WISP-2, indicators of canonical Wnt signaling, between Sfrp5-/- and WT mice. In contrast, phosphorylation of c-Jun N-terminal kinase (JNK), a downstream target of the noncanonical Wnt signaling, was elevated in white adipose tissue in Sfrp5-/- mice. Also, the phosphorylation of c-Jun, a downstream substrate of JNK, was elevated in Sfrp5-/- mice compared with WT mice.
Formal Description
Interaction-ID: 9201

gene/protein

SFRP5

NOT affects_expression of

gene/protein

CCN5

in epididymal adipose tissues; after high-fat high-sucrose diet
Comment To analyze the downstream signaling pathways affected by Sfrp5 deficiency, the authors assessed whether the canonical or noncanonical Wnt signaling pathways were activated in epididymal adipose tissues of Sfrp5-/- and WT mice fed a high fat high sucrose diet. No differences were detected in transcript expression of cyclin D1 or WISP-2, indicators of canonical Wnt signaling, between Sfrp5-/- and WT mice. In contrast, phosphorylation of c-Jun N-terminal kinase (JNK), a downstream target of the noncanonical Wnt signaling, was elevated in white adipose tissue in Sfrp5-/- mice. Also, the phosphorylation of c-Jun, a downstream substrate of JNK, was elevated in Sfrp5-/- mice compared with WT mice.
Formal Description
Interaction-ID: 9202

gene/protein

SFRP5

NOT affects_activity of

in epididymal adipose tissues; after high-fat high-sucrose diet
Comment To analyze the downstream signaling pathways affected by Sfrp5 deficiency, the authors assessed whether the canonical or noncanonical Wnt signaling pathways were activated in epididymal adipose tissues of Sfrp5-/- and WT mice fed a high fat high sucrose diet. No differences were detected in transcript expression of cyclin D1 or WISP-2, indicators of canonical Wnt signaling, between Sfrp5-/- and WT mice. In contrast, phosphorylation of c-Jun N-terminal kinase (JNK), a downstream target of the noncanonical Wnt signaling, was elevated in white adipose tissue in Sfrp5-/- mice. Also, the phosphorylation of c-Jun, a downstream substrate of JNK, was elevated in Sfrp5-/- mice compared with WT mice.
Formal Description
Interaction-ID: 9203

gene/protein

SFRP5

affects_phosphorylation of

gene/protein

MAPK8

in epididymal adipose tissues; after high-fat high-sucrose diet
Drugbank entries Show/Hide entries for MAPK8
Comment To analyze the downstream signaling pathways affected by Sfrp5 deficiency, the authors assessed whether the canonical or noncanonical Wnt signaling pathways were activated in epididymal adipose tissues of Sfrp5-/- and WT mice fed a high fat high sucrose diet. No differences were detected in transcript expression of cyclin D1 or WISP-2, indicators of canonical Wnt signaling, between Sfrp5-/- and WT mice. In contrast, phosphorylation of c-Jun N-terminal kinase (JNK), a downstream target of the noncanonical Wnt signaling, was elevated in white adipose tissue in Sfrp5-/- mice. Also, the phosphorylation of c-Jun, a downstream substrate of JNK, was elevated in Sfrp5-/- mice compared with WT mice.
Formal Description
Interaction-ID: 9204

gene/protein

SFRP5

affects_phosphorylation of

gene/protein

JUN

in epididymal adipose tissues; after high-fat high-sucrose diet
Drugbank entries Show/Hide entries for JUN
Comment To analyze the downstream signaling pathways affected by Sfrp5 deficiency, the authors assessed whether the canonical or noncanonical Wnt signaling pathways were activated in epididymal adipose tissues of Sfrp5-/- and WT mice fed a high fat high sucrose diet. No differences were detected in transcript expression of cyclin D1 or WISP-2, indicators of canonical Wnt signaling, between Sfrp5-/- and WT mice. In contrast, phosphorylation of c-Jun N-terminal kinase (JNK), a downstream target of the noncanonical Wnt signaling, was elevated in white adipose tissue in Sfrp5-/- mice. Also, the phosphorylation of c-Jun, a downstream substrate of JNK, was elevated in Sfrp5-/- mice compared with WT mice.
Formal Description
Interaction-ID: 9205

gene/protein

SFRP5

affects_activity of

in epididymal adipose tissues; after high-fat high-sucrose diet
Comment Activation of JNK1 promotes insulin resistance through serine phosphorylation of insulin receptor substrate 1 (IRS-1). IRS-1 phosphorylation at residue Ser307 was increased in fat tissue of Sfrp5-/- mice compared with WT mice.
Formal Description
Interaction-ID: 9206

gene/protein

SFRP5

affects_phosphorylation of

gene/protein

IRS1

in adipose tissue; after high-fat high-sucrose diet, at Ser307 of IRS1
Drugbank entries Show/Hide entries for IRS1
Comment Activation of JNK1 promotes insulin resistance through serine phosphorylation of insulin receptor substrate 1 (IRS-1). IRS-1 phosphorylation at residue Ser307 was increased in fat tissue of Sfrp5-/- mice compared with WT mice.
Formal Description
Interaction-ID: 9207

gene/protein

SFRP5

affects_activity of

disease

Insulin resistance

in adipose tissue; after high-fat high-sucrose diet
Comment The insulin signaling in adipose tissue was assessed by measuring the activating phosphorylation of Akt at Ser473 after systemic insulin administration. In WT mice fed a high fat high sucrose diet, insulin stimulated the phosphorylation of Akt in fat pads, but this induction of phosphorylation was diminished in the high fat high sucrose diet-fed Sfrp5-/- mice.
Formal Description
Interaction-ID: 9208

gene/protein

SFRP5

affects_phosphorylation of

gene/protein

AKT1

in adipose tissue; after high-fat high-sucrose diet, at Ser473 of AKT1, after insulin stimulation
Drugbank entries Show/Hide entries for AKT1
Comment The insulin signaling in adipose tissue was assessed by measuring the activating phosphorylation of Akt at Ser473 after systemic insulin administration. In WT mice fed a high fat high sucrose diet, insulin stimulated the phosphorylation of Akt in fat pads, but this induction of phosphorylation was diminished in the high fat high sucrose diet-fed Sfrp5-/- mice.
Formal Description
Interaction-ID: 9215

gene/protein

SFRP5

affects_activity of

in adipose tissue; after high-fat high-sucrose diet, at Ser473 of AKT1, after insulin stimulation
Comment The impaired insulin sensitivity and enhanced adipose tissue inflammation in Sfrp5-/- mice can be attributed to enhanced activation of JNK1.
Formal Description
Interaction-ID: 9216

gene/protein

SFRP5

affects_activity of

phenotype

decreased insulin sensitivity

in adipose tissue
Comment The acute administration of Sfrp5 to models of obese and diabetic mice improved metabolic function and reduced adipose tissue inflammation.
Formal Description
Interaction-ID: 9219

gene/protein

SFRP5

decreases_activity of

in adipose tissue; in obese and diabetic mice