That is one conclusion drawn by researchers at the Salk Institute for Biological Studies, who recently showed that mice lacking a gene regulating energy balance are protected from weight gain, even on a high fat diet.
These findings have implications for the worldwide obesity epidemic and its consequences, such as type two diabetes.
In the December 16, 2010 issue of Nature, a team led by Marc Montminy, M.D., Ph.D, professor in the Clayton Foundation Laboratories for Peptide Biology, reports that a gene known as CRTC3 decreases energy expenditure by fat cells.
"Ideas about obesity are based on concepts of feast or famine," said Montminy. "As humans, we developed ways of coping with famine by expressing genes like CRTC3 to slow the rate of fat burning. Individuals with these active 'thrifty genes' had an advantage -- they could survive long periods without food."
Back in the 1960's, scientists theorized humans had specialized genes that slowed our fat-burning capabilities. During prehistoric times, these genes were crucial to our survival, as we never knew when, or how much, we were going to eat on any given day.
Fast forward to 2010, when finding food has never been easier. We don't need those ancient genes anymore, but our bodies haven't gotten the memo.
To analyze its role in fat metabolism, the researchers bred mice lacking the CRTC3 gene and put them on varying diets -- some moderate, some high fat.
Normal mice and the mice lacking the CRTC3 gene appeared similar when fed a moderate fat diet. But when fed the mouse version of the Philly cheese steak diet, only the normal mice became obese.
The mice lacking CFTC3 stayed slim and didn't gain weight.
"They also had about twice as many brown fat cells than did normal mice," said Montminy.
Our bodies also have two different types of fat cells -- white and brown; bad and good.
The white fat cells (also called WAT for "white adipose tissueâ€) serves as fat storage about bellies and hips -- that's the bad stuff.
However, the brown fat (BAT; "brown adipose tissue") is downright desirable.
"Brown fat is very different from white fat," says Youngsup Song, Ph.D., a postdoctoral fellow in the Montminy lab and the study's first author.
According to Song, brown fat tissue burns fat that has accumulated in white fat tissue to generate heat as a way to maintain body temperature.
In fact, some evidence suggests that humans with a genetic propensity to leanness have more brown fat cells than do "ample" individuals.
As desirable as that trait may seem now, those folks likely struggled mightily to stay alive during the Paleolithic era.
Although the researchers found that CRTC3 loss also perturbs how all fat cells respond to brain signals controlling energy expenditure, they remain particularly intrigued by the brown fat connection.
"CRTC3 could be a switch controlling the number of brown fat cells, " says Montminy. "That is key, because if you could make more brown adipocytes, you could potentially control obesity."
What about humans?
This is all well and good for mice, but what about people?
To explore how relevant these studies are to humans, Montminy asked clinicians at Cedars-Sinai Medical Center in Los Angeles to search databases of patient genetic information for a particularly interesting human CRTC3 gene mutation, which appeared to represent a more potent form of the normal gene.
Since mice lacking CRTC3 resist obesity, the researchers figured humans carrying a revved-up version of the gene might show the opposite tendency.
Indeed. genetic testing of two groups of Mexican-American patients revealed that individuals harboring the active CRTC3 mutation showed increased incidence of obesity.
"This is an example in which findings from rodent research led to a novel discovery in humans," says Mark Goodarzi, M.D., Ph.D., an endocrinologist at Cedars-Sinai and collaborator in the study. "Not all Mexican-American individuals with the variant will develop obesity, but those carrying it are at higher risk."
Interestingly, non-Hispanic Caucasians carrying the variant do not show increased obesity, a difference likely related to environmental or lifestyle factors.
Overall this study illustrates an important principle: that what is genetically advantageous in one cultural or historic context may not be in another.
In fact, Montminy does not view obesity as an aberration or a "disease."
"Storing fat in adipose tissue is a normal response. A lot people are obese but do not develop type 2 diabetes," he says, suggesting that genes like CRTC3 could serve as diagnostic tools as well as drug targets.