General Information:

Id: 654
Diseases: Diabetes mellitus, type II - [OMIM]
Fatty liver disease, nonalcoholic
Insulin resistance
Obesity - [OMIM]
Mammalia
review
Reference: Chen HC and Farese RV Jr(2005) Inhibition of triglyceride synthesis as a treatment strategy for obesity: lessons from DGAT1-deficient mice. Arterioscler. Thromb. Vasc. Biol. 25: 482-486 [PMID: 15569818]

Interaction Information:

Comment The final step in triacylglycerol (TAG) synthesis is catalyzed by one of two known DGAT enzymes, DGAT1 or DGAT2. Both enzymes can use a variety of fatty acyl CoA substrates, although DGAT1 appears to prefer the mono-unsaturated oleoyl CoA over the saturated palmitoyl CoA.
Formal Description
Interaction-ID: 3459

gene/protein

DGAT1

increases_activity of

process

triglyceride biosynthetic process

Comment Triglycerides synthesized by DGAT enzymes are either stored in cytosolic lipid droplets or, in some organs such as the liver and small intetine, secreted as components of lipoproteins.
Formal Description
Interaction-ID: 3461

gene/protein

DGAT1

increases_quantity of

drug/chemical compound

Triacylglycerol

in cytosolic lipid droplets
Comment Newborn DGAT2-deficient mice (Dgat2-/-) are smaller than wild-type controls and die within hours after birth. Carcass triglyceride content is severely reduced, and the mice therefore lack essential fatty acids, which results in abnormalities in skin lipids and impaired epidermal barrier function.
Formal Description
Interaction-ID: 3464

gene/protein

DGAT2

affects_activity of

phenotype

abnormal skin lipids

Comment In a mixed genetic background, DGAT2+/- mice are not protected from diet-induced obesity, suggesting that a 50 % reduction of DGAT2 expression is not limiting for triglyceride synthesis.
Formal Description
Interaction-ID: 3468

gene/protein

DGAT2

NOT affects_activity of

disease

Obesity

if DGAT2 is 50% reduced
Comment In contrast to DGAT2-/- mice, DGAT1-deficient DGAT1-/- mice are viable and have more modest reductions in tissue triglycerides.
Formal Description
Interaction-ID: 3469

gene/protein

DGAT1

NOT affects_activity of

process

determination of adult lifespan

Comment Adult DGAT-/- mice have about 50 % less adipose mass and smaller adipocytes than wild-type mice on a chow diet.
Formal Description
Interaction-ID: 3477

gene/protein

DGAT

affects_quantity of

tissue/cell line

adipose tissue

on chow diet
Comment Although tissue triglyceride levels are reduced in DGAT1-/- mice, the levels of diacylglycerol and fatty acyl CoA, substrates of the DGAT reaction, are not significantly elevated and tended to be lower in skeletal muscle and livers of DGAT1-/- mice.
Formal Description
Interaction-ID: 3479

gene/protein

DGAT1

NOT affects_quantity of

drug/chemical compound

Diacylglycerol

Comment When fed a high fat diet, DGAT1-/- mice are resistant to weight gain, and inbred DGAT1-heterozygous (DGAT1+/-) mice have an intermediate phenotype.
Formal Description
Interaction-ID: 3482

gene/protein

DGAT1

affects_activity of

disease

Obesity

on high-fat diet
Comment DGAT1-/- mice are also protected from diet-induced hepatic steatosis.
Formal Description
Interaction-ID: 3484

gene/protein

DGAT1

affects_activity of

disease

Fatty liver disease, nonalcoholic

Comment Correlating with the decrease in adiposity, insulin sensitivity is increased in DGAT1-/- mice.
Formal Description
Interaction-ID: 3485

gene/protein

DGAT1

affects_activity of

phenotype

increased insulin sensitivity

Comment Insulin-stimulated glucose transport is increased in skeletal muscle and white adipose tissue of DGAT1-/- mice, and insulin-stimulated activities of phosphatidylinositol-3 kinase, protein kinase B, and protein kinase C-delta, three key molecules in the insulin signaling pathway, are also increased in the skeletal muscle of DGAT1-/- mice.
Formal Description
Interaction-ID: 3506

gene/protein

DGAT1

affects_activity of

process

glucose import

in skeletal muscle; in white adipose tissue; if stimulated by insulin
Comment Insulin-stimulated glucose transport is increased in skeletal muscle and white adipose tissue of DGAT1-/- mice, and insulin-stimulated activities of phosphatidylinositol-3 kinase, protein kinase B, and protein kinase C-delta, three key molecules in the insulin signaling pathway, are also increased in the skeletal muscle of DGAT1-/- mice.
Formal Description
Interaction-ID: 3508

gene/protein

DGAT1

affects_activity of

complex/PPI

Phosphatidylinositol 3-kinase

in skeletal muscle; if stimulated by insulin
Comment Insulin-stimulated glucose transport is increased in skeletal muscle and white adipose tissue of DGAT1-/- mice, and insulin-stimulated activities of phosphatidylinositol-3 kinase, protein kinase B, and protein kinase C-delta, three key molecules in the insulin signaling pathway, are also increased in the skeletal muscle of DGAT1-/- mice.
Formal Description
Interaction-ID: 3511

gene/protein

DGAT1

affects_activity of

gene/protein

AKT1

in skeletal muscle; if stimulated by insulin
Drugbank entries Show/Hide entries for AKT1
Comment Insulin-stimulated glucose transport is increased in skeletal muscle and white adipose tissue of DGAT1-/- mice, and insulin-stimulated activities of phosphatidylinositol-3 kinase, protein kinase B, and protein kinase C-delta, three key molecules in the insulin signaling pathway, are also increased in the skeletal muscle of DGAT1-/- mice.
Formal Description
Interaction-ID: 3513

gene/protein

DGAT1

affects_activity of

gene/protein

PRKCD

in skeletal muscle; if stimulated by insulin
Drugbank entries Show/Hide entries for PRKCD
Comment Insulin-stimulated glucose transport is increased in skeletal muscle and white adipose tissue of DGAT1-/- mice, and insulin-stimulated activities of phosphatidylinositol-3 kinase, protein kinase B, and protein kinase C-delta, three key molecules in the insulin signaling pathway, are also increased in the skeletal muscle of DGAT1-/- mice.
Formal Description
Interaction-ID: 3515

gene/protein

DGAT1

affects_activity of

process

insulin receptor signaling pathway

in skeletal muscle; if stimulated by insulin
Comment In DGAT1-/- mice decreased levels of serine-phosphorylated insulin receptor substrate-1, a molecule implicated in insulin resistance, were observed in the skeletal muscle and white adipose tissue.
Formal Description
Interaction-ID: 3516

gene/protein

DGAT1

affects_activity of

gene/protein

IRS1

Drugbank entries Show/Hide entries for IRS1
Comment DGAT1-/- mice lose more weight than wild-type mice in response to subcutaneous leptin infusion, consistent with increased leptin sensitivity.
Formal Description
Interaction-ID: 3517

gene/protein

DGAT1

affects_activity of

process

response to leptin

Comment DGAT1 deficiency affects the expression and secretion of several adipocyte-derived factors that modulate energy and glucose metabolism.
Formal Description
Interaction-ID: 3518

gene/protein

DGAT1

affects_activity of

process

glucose metabolic process

Comment The final step in triacylglycerol (TAG) synthesis is catalyzed by one of two known DGAT enzymes, DGAT1 or DGAT2. Both enzymes can use a variety of fatty acyl CoA substrates, although DGAT1 appears to prefer the mono-unsaturated oleoyl CoA over the saturated palmitoyl CoA.
Formal Description
Interaction-ID: 13011

gene/protein

DGAT2

increases_activity of

process

triglyceride biosynthetic process

Comment Triglycerides synthesized by DGAT enzymes are either stored in cytosolic lipid droplets or, in some organs such as the liver and small intetine, secreted as components of lipoproteins.
Formal Description
Interaction-ID: 13013

gene/protein

DGAT2

increases_quantity of

drug/chemical compound

Triacylglycerol

in cytosolic lipid droplets
Comment Triglycerides synthesized by DGAT enzymes are either stored in cytosolic lipid droplets or, in some organs such as the liver and small intetine, secreted as components of lipoproteins.
Formal Description
Interaction-ID: 13014

gene/protein

DGAT2

increases_quantity of

complex/PPI

Lipoprotein

in liver, in small intestine
Comment Triglycerides synthesized by DGAT enzymes are either stored in cytosolic lipid droplets or, in some organs such as the liver and small intetine, secreted as components of lipoproteins.
Formal Description
Interaction-ID: 13015

gene/protein

DGAT1

increases_quantity of

complex/PPI

Lipoprotein

in liver, in small intestine
Comment Newborn DGAT2-deficient mice (Dgat2-/-) are smaller than wild-type controls and die within hours after birth. Carcass triglyceride content is severely reduced, and the mice therefore lack essential fatty acids, which results in abnormalities in skin lipids and impaired epidermal barrier function.
Formal Description
Interaction-ID: 13020

gene/protein

DGAT2

affects_activity of

phenotype

impaired skin barrier function

Comment Newborn DGAT2-deficient mice (Dgat2-/-) are smaller than wild-type controls and die within hours after birth. Carcass triglyceride content is severely reduced, and the mice therefore lack essential fatty acids, which results in abnormalities in skin lipids and impaired epidermal barrier function.
Formal Description
Interaction-ID: 13028

gene/protein

DGAT1

affects_activity of

phenotype

impaired skin barrier function

Comment Newborn DGAT2-deficient mice (Dgat2-/-) are smaller than wild-type controls and die within hours after birth. Carcass triglyceride content is severely reduced, and the mice therefore lack essential fatty acids, which results in abnormalities in skin lipids and impaired epidermal barrier function.
Formal Description
Interaction-ID: 13031

gene/protein

DGAT2

affects_activity of

process

determination of adult lifespan

Comment Although tissue triglyceride levels are reduced in DGAT1-/- mice, the levels of diacylglycerol and fatty acyl CoA, substrates of the DGAT reaction, are not significantly elevated and tended to be lower in skeletal muscle and livers of DGAT1-/- mice.
Formal Description
Interaction-ID: 13037

gene/protein

DGAT1

NOT affects_quantity of

drug/chemical compound

Fatty acid acyl-CoA

Comment In DGAT1-/- mice decreased levels of serine-phosphorylated insulin receptor substrate-1, a molecule implicated in insulin resistance, were observed in the skeletal muscle and white adipose tissue.
Formal Description
Interaction-ID: 13040

gene/protein

DGAT1

affects_activity of

disease

Insulin resistance

Comment DGAT1 deficiency affects the expression and secretion of several adipocyte-derived factors that modulate energy and glucose metabolism.
Formal Description
Interaction-ID: 13041

gene/protein

DGAT1

affects_activity of

process

energy homeostasis