February 16, 2018 Comments (0) Views: 1568 Biotech, Blog

UC San Diego Researches Figure Out What Derails Weight Loss Efforts

Scientists at the Institute for Diabetes and Metabolic Health say an enzyme may be key

Many people who’ve tried to lose weight and keep it off know it’s often times easier said than done. Science backs this up. You may remember a study last year where researchers checked in with 14 Biggest Loser contestants six years after their appearance on the show and most had gained back the majority of the weight they’d worked so hard to shed. But, it wasn’t due to a lack of willpower. Contestants’ metabolisms had slowed considerably. Now scientists at UC San Diego say they may have figured out exactly what causes calorie-burning to taper off and those stubborn plateaus to persist during weight loss efforts.

The study, published in Cell on February 8, attributes both frustrating phenomena to an enzyme called TANK-binding kinase 1, which the researchers say is a key player in burning calories. In mouse models, researchers observed a double whammy. Obesity-triggered chronic stress activates a pathway inducing TBK1 and other genes associated with obesity and inflammation. TBK1 shuts down one of the master regulators of energy expenditure, which in turn reduces a cell’s ability to burn calories and causes fat to be stored.

“Human bodies are very efficient at storing energy by repressing energy expenditure to conserve it for later when you need it,” said Alan Saltiel, PhD, director of the UC San Diego Institute for Diabetes and Metabolic Health. “This is nature’s way of ensuring that you survive if a famine comes.”

However, getting rid of TBK1 might not be the best solution. Saltiel said doing so in obese mice resulted in weight loss, but actually increased inflammation. In normal weight mice, there was no change.

“Inhibiting TBK1 has the potential to restore energy balance in states of obesity by enhancing the ability to burn some fat,” Saltiel said. “This is probably not the only pathway accounting for energy expenditure in fasting or obesity, but this information provides new insight into how we might develop drugs that inhibit TBK1 or other enzymes involved in metabolism.”

Saltiel and his team had already looked into one TBK1 inhibitor called amlexanox that’s also anti-inflammatory. It was developed in Japan in the 1980s to treat asthma. When given to obese mice, amlexanox helped them shed excess weight and also increased their sensitivity to insulin, a factor in diabetes and fatty liver disease.

“I think you’ll probably still have to do both: reduce energy intake through diet and increase energy expenditure by blocking this compensatory reduction in burning calories. We know that diets alone don’t work and this is why,” Saltiel said.