Scientists at the University of California, Berkeley have realised that a cartain enzyme-deficiency could prevent obesity despite enormous consumption of food. The enzyme in question is responsible for controlling the breakdown of fat.
The researchers said that in a study conducted by them, mice that had this enzyme disabled remained lean despite eating a high-fat diet, and losing a hormone that suppresses appetite.
Advertisement"We have discovered a new enzyme within fat cells that is a key regulator of fat metabolism and body weight, making it a promising target in the search for a treatment for human obesity," Nature magazine quoted Hei Sook Sul, UC Berkeley professor of nutritional sciences and toxicology and principal investigator of the research, as saying.
The researchers revealed that the enzyme called adipose-specific phospholipase A2 (AdPLA) is found in abundance only in fat tissue.
According to them, it sets off a chain of events that increases levels of a signalling molecule called prostaglandin E2 (PGE2), which suppresses the breakdown of fat.
During the study, the researchers observed that mice lacking AdPLA had lower PGE2 levels and a higher rate of fat metabolism.
"When levels of PGE2 are decreased because of the lack of AdPLA, fat breakdown proceeds unchecked, resulting in leanness even in animals that eat all day long," said post-doctoral fellow Robin Duncan, co-lead author of the study.
For their research, the research team compared mice that had had the gene for AdPLA expression knocked out with a control group of normal mice.
As soon as the mice were weaned at about 3 weeks of age, the researchers began offering the two groups of mice an all-you-can-eat buffet of tasty, high-fat foods.
The researchers observed that the enzyme did not seem to affect appetite, as the two groups ate equivalent amounts. However, the disparity in weight gain became clear as the mice grew older.
The group revealed that by 64 weeks of age, considered the twilight years in a lab mouse's lifespan, the mice that lacked the AdPLA enzyme averaged only 39.1 grams, a weight more typical of a low-fat diet, while the control mice weighed in at a hefty 73.7 grams.
In their study report, the researcher noted the missing AdPLA did not change the number of fat cells, but simply kept the cells from accumulating excess fat.
They also studied whether loss of AdPLA could prevent genetic obesity in mice by comparing the animals lacking leptin, the hormone that signals when the body is full, with those lacking both AdPLA and leptin.
Leptin was taken into account because its deficiency is known to make mice voracious eaters, which typically consuming two to three times more food per day than their normal counterparts, and consequently develop obesity.
During the study, leptin-deficient mice ate an average of 5 grams of food per day, while mice that lacked both AdPLA and leptin ate 7.5 grams. Normal mice would generally eat only 2-3 grams per day.
By 17 weeks of age, the leptin-deficient mice were already hitting the scales at 75 grams, while those lacking both AdPLA and leptin weighed just under 35 grams.
The team noted that levels of AdPLA increase after eating to block fat breakdown, and decrease with fasting to allow fat breakdown to proceed efficiently. They also found discovered AdPLA levels to be higher in obese mice.
"This means that local signals in fat tissue allow fat cells to directly regulate fuel provision for the body, which changes our fundamental understanding of how the body regulates fat breakdown. We found that mice deficient in AdPLA expend more energy than normal mice, and they also burn more fat directly within fat cells," said graduate student Maryam Ahmadian, another study co-lead author.
While the new findings appear to be very significant, the researchers caution that previous discoveries in fat metabolism and appetite regulation have not always translated well from mice to humans.
Even though some people have mutations in the gene that codes for AdPLA, the researchers insist that it has yet to be e seen what effect such mutations have in humans.