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Scientists report the discovery of a previously unknown gene family that plays a key role in whether or not cells store fat, a discovery that could lead to new approaches to obesity and related diseases.
Dr. David L. Silver states that, "Since the ability to store fat in lipid droplets within cells is a fundamental process in all eukaryotic life from the simplest (baker’s yeast) to complex (e.g. humans), we searched for genes that encoded for proteins that were involved in fat storage and had to be evolutionarily conserved in all eukaryotic organisms."
He and colleagues from Albert Einstein College of Medicine, Bronx, identified two such genes, which they named FIT1 and FIT2 for fat-inducing transcript.
"Our experiments demonstrate that FIT proteins are not involved in synthesizing fat but are involved in packaging fat into lipid droplets as demonstrated both in cell culture experiments and in mice. This is a very unique activity among proteins," Dr. Silver explained.
According to a report in the PNAS Early Edition posted online December 17, over expression of the FIT genes in human cells led to a dramatic increase in fat storage, whereas silencing the FIT genes in mouse cells led to an equally impressive decrease in lipid droplets.
In a further experiment, the scientists found that silencing the FIT genes in zebra fish resulted in fish that stored less fat than a control group, despite being fed a high-fat diet.
Dr. Silver reported that, "Since the FIT proteins play a primary role in storing fat, we are very interested in exploring the possibility that FITs might be suitable drug targets to treat obesity and obesity-associated diseases."
PNAS Early Edition 2007.
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FACT:
Metformin, contra-indications: Patients treated with metformin should have metformin withheld in presence of poor renal function. A new study aimed to establish pragmatic effective glomular filtration rate (GFR) limits for use in patients being considered for metformin treatment. The study proposes pragmatic estimated GFR (eGFR) thresholds for metformin treatment to replace the currently recommended serum creatinine levels of 130 or 150 mmol/l. Chronic kidney disease (CKD) stages four or five would be an absolute contra indication to metformin treatment while the presence of CKD stage 3 (eGFR 30 – 59 ml/min/1.73 m2) should alert clinicians to consider other risk factors before initiating or continuing treatment. Diabetic Medicine,24 (1160-1163)
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