Congenital disease linked to adipocyte development

Congenital disease linked to adipocyte development
Some patients with congenital generalized lipodystrophy, who lack adipocytes and develop severe insulin resistance, have a defect in adipocyte development that can be partially reversed, according to a study published online Aug. 28 in Diabetes.

(HealthDay)—Some patients with congenital generalized lipodystrophy (CGL), who lack adipocytes and develop severe insulin resistance, have a defect in adipocyte development that can be partially reversed, according to a study published online Aug. 28 in Diabetes.

To identify the defect in adipogenesis in patients with CGL due to mutations in AGPAT2, Angela R. Subauste, M.D., from the University of Michigan in Ann Arbor, and colleagues studied adipogenesis using 3T3-L1 preadipocytes with knockdown or of AGPAT2, as well as muscle-derived multipotent cells from controls and from patients harboring AGPAT2 mutations.

The researchers found that individuals with mutated AGPAT2 had an adipogenic defect which was rescued by a retrovirus expressing AGPAT2. Inducing adipogenesis led to increased cell death in the absence of AGPAT2. Akt activation was reduced by lack of AGPAT2, and lipogenesis was partially restored by overexpression of constitutively active AKT. AGPAT2 modulated the lipome, altering activation of the phosphatidylinositol 3-kinase/Akt and peroxisome proliferator-activated receptor gamma (PPARγ) pathways. The adipogenic defect in CGL cells was partially rescued by the PPARγ agonist pioglitazone.

"Our findings demonstrate that CGL secondary to AGPAT2 mutation is not a disease of empty adipocytes, rather a disease of defective adipose due to a disruption in the modulation of the lipome during adipogenesis," Subauste and colleagues conclude.

More information: Abstract
Full Text (subscription or payment may be required)

add to favorites email to friend print save as pdf

Related Stories

Fat-free diet reduces liver fat in fat-free mice

Feb 03, 2009

Researchers at UT Southwestern Medical Center have uncovered crucial clues about a paradoxical disease in which patients with no body fat develop many of the health complications usually found in obese people.

Researchers find more clues to causes of breast cancer

Oct 27, 2011

Publishing in the current issue of The Journal of Biological Chemistry (Vol. 286, No 43), researchers at Moffitt Cancer Center in Tampa, Fla., have discovered additional mechanisms of "Akt" activation and suggest a component ...

Recommended for you

Magnesium cuts diabetes risk

5 hours ago

Getting enough magnesium in the diet may reduce the risk of diabetes, especially for those who already show signs of heading that way.

Personalised treatment for stress-related diabetes

Oct 14, 2014

Researchers at Lund University in Sweden are testing a treatment for type 2 diabetes which targets the disease mechanism itself - and not just the symptoms. For the first time, knowledge about the individual patient's genetic ...

Sensors to simplify diabetes management

Oct 13, 2014

For many patients diagnosed with diabetes, treating the disease can mean a burdensome and uncomfortable lifelong routine of monitoring blood sugar levels and injecting the insulin that their bodies don't ...

Androgen receptor signaling tied to insulin resistance

Oct 09, 2014

(HealthDay)—Mouse models show tissue-specific androgen receptor (AR) signaling is involved in regulation of metabolism, which may explain the link between androgen deprivation therapy (ADT) and the development ...

User comments