Lack of the protein ankyrin-B contributes to obesity
What is the chief culprit of obesity? There are various possible answers, such as a high fat, high cholesterol diet, and a sedentary lifestyle. However, things are not so simple. In fact, some individuals are more prone to obesity because of their genetic makeup.
Two researchers from Duke University, Dr. Damaris Lorenzo and Dr. Vann Bennett, have demonstrated in mice that inactivation of the ankyrin-B (AnkB) gene leads to cell-autonomous adiposity. Their findings are summarised in a paper titled "Cell-autonomous adiposity through increased cell surface GLUT4 due to ankyrin-B deficiency," appearing in the Proceedings of the National Academy of Sciences (PNAS).
The PNAS study shows that adipose tissue-specific AnkB-KO mice are more likely to develop obesity with age or on a high fat diet. Further, AnkB deficiency leads to increased cell surface glucose transporter type 4 (GLUT4)
, resulting in increased glucose uptake and lipid accumulation in adipocytes (also known as lipocytes and fat cells).
AnkB belongs to a family of ankyrin proteins, which interact with many membrane proteins like channels and transporters. AnkB ensures that these channels and transporters are in their proper locations in the cell membrane. GLUT4 is an important glucose transporter found in adipose tissues and striated muscle, which is responsible for insulin-regulated glucose storage.
In 2015, Dr. Bennett, Dr. Lorenzo, and collaborators found that AnkB promotes internalization of GLUT4 from the plasma membrane, and AnkB-deficient mice exhibited significant increases in cell surface GLUT4 and in glucose uptake in adipocytes. The study "Ankyrin-B metabolic syndrome combines age-dependent adiposity with pancreatic β cell insufficiency" appears in the Journal of Clinical Investigation.
The new study confirms that loss of AnkB alters the dynamics of GLUT4. Specifically, impaired function of AnkB results in persistent cell surface GLUT4, allowing more glucose to flow into cells. Increased glucose uptake promotes lipogenesis, leading to obesity.
A certain percentage of the population has AnkB variants that cause AnkB reduction. This leads to a hyperthesis that these people may be more susceptible to obesity. In the new study, Dr. Bennett and Dr. Lorenzo proved that fat cells carrying these variants indeed showed higher glucose uptake.
In conclusion, the study demonstrates that AnkB loss contributes to obesity through increasing cell surface GLUT4 and that certain AnkB variants may be genetic risk factors for obesity. The study would inform novel treatment strategies for obesity.