Congenital disease linked to adipocyte development

September 7, 2012
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.

Explore further: Researchers find more clues to causes of breast cancer

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

Related Stories

Researchers find more clues to causes of breast cancer

October 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

Smart mat detects early warning signs of foot ulcers

August 16, 2017
While completing his residency in anesthesiology at Massachusetts General Hospital in the mid-2000s, Jon Bloom saw his fair share of foot amputations among patients with diabetes. The culprit: infected foot ulcers.

The best place to treat type 1 diabetes might be just under your skin

August 14, 2017
A group of U of T researchers have demonstrated that the space under our skin might be an optimal location to treat type 1 diabetes (T1D).

New measure of insulin-making cells could gauge diabetes progression, treatment

August 10, 2017
Researchers at the University of Wisconsin-Madison have developed a new measurement for the volume and activity of beta cells, the source of the sugar-regulating hormone insulin.

Pioneering immunotherapy shows promise in type 1 diabetes

August 9, 2017
It may be possible to 'retrain' the immune system to slow the progression of type 1 diabetes, according to results of a clinical trial published today in the journal Science Translational Medicine.

Online team-based game helps patients with diabetes lower blood glucose

August 8, 2017
Researchers from Brigham and Women's Hospital and the Veterans Affairs Boston Healthcare System have found that an online, team-based game designed to teach patients about diabetes self-management had a sustained and meaningful ...

Oxidative stress biomarkers don't always signal diabetes risk

August 7, 2017
High levels of compounds found in the body that are commonly associated with oxidative damage may actually be a good sign for some people, according to a recent review of multiple human studies led by an epidemiologist at ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.