Next Generation: Fat-Targeted Gene Knockdown

Obesity is a term that means you weigh at least 20% more than what is considered abnormal weight for your height. Extra weight makes you more likely to have high blood pressure and high cholesterol. Both of those conditions make heart disease or stroke more likely.Obesity can also affect your quality of life and lead to psychological problems, such as low self-esteem or depression.Taking steps to tackle obesity is important because, in addition to causing obvious physical changes.

Most drugs developed to treat obesity have focused on reducing appetite by manipulating signals in the gastrointestinal tract or central nervous system. These approaches have had limited success, and sometimes produce problematic side effects—the appetite suppressant sibutramine, for example, was pulled from the market in 2010 because it increased patients’ risk of strokes and heart attacks

Controlling metabolism and immune responses by directly targeting fat cells, or adipocytes, is a more attractive strategy, but has been hampered by an inability to precisely and effectively deliver small molecules to adipose tissue. Previous attempts at gene therapy in adipocytes have employed viral vectors, which have led to unchecked expression with potentially harmful effects.

Researchers produced a molecular complex containing ATS oligopeptides bound to expression vectors for a short-hairpin RNA directed against the FABP4 gene, which encodes a fatty acid binding protein that affects lipid storage in adipocytes. When the researchers injected this complex into mice on a high-fat diet, they saw a 20 percent decrease in body weight, as well as improved glucose tolerance and insulin sensitivity, after seven weeks of treatment.

A specific short peptide aimed at fat cells can deliver a DNA sequence that knocks down expression of a key fatty acid binding protein. The method provides a new way to study the functions of adipocytes—a notoriously intractable cell type—and suggests an avenue for gene therapy to combat obesity in humans.  

with love

-Dixy