As much of the US population stares in dismay at its newly expanded waistline - yet another holiday season acquisition that somehow needs to be dealt with - science has some answers about how those unwanted pounds get there that may in time lead to ideas about how to get rid of them more easily.

In the combined Dec. 21 and 28, 2006 issue of Nature, researchers from Washington University in St. Louis presented both animal and human studies that demonstrate a relationship between gut flora composition and body weight.

Certain types of bacteria may be able to break down food more efficiently, leading to more efficient energy extraction and higher body weights for their unfortunate owners.

And in January 2007 issue of Cell Metabolism, researchers present new findings on the other side of the coin. The molecular mechanism that leads to hunger as a consequence of reduced food intake.

The Nature papers describe intriguing relationships of two types of bacteria to each other, and to weight: the bacterioides and the firmicutes. If senior author Jeffrey Gordon and his colleagues are correct, the firmicutes seem to be quite misnamed. When they inhabit the gut, they appear to contribute to the development of flab.

Gordon and his colleagues conducted experiments in mice showing that obese mice had a higher proportion of firmicutes in their feces. The firmicutes, Gordon and his colleagues wrote in their paper, convey upon their owners an increased capacity to harvest energy from the diet.' Apparently, they encode enzymes that enable the firmicutes to digest polysaccharides that the bacteroides can't get at. That leads to the extraction of more calories from food by the firmicutes.

In a set of transplantation experiments, Gordon and his colleagues further showed that the obesity was transmissible. When the researchers colonized germ-free mice with gut bacteria from either obese or lean mice, the recipients of obese-type gut bacteria gained more weight than those that received lean-type gut microbes. Gordon and his team concluded that, taken together, the findings provide evidence that the gut microbiome should be considered as a set of genetic factors that, together with host genotype and lifestyle (energy intake and expenditure), contribute to the pathophysiology of obesity.'

In a separate brief article in the same issue of Nature, Gordon and his colleagues sequenced the gut bacteria of a dozen obese individuals who were on either a low-fat or low-carbohydrate calorie-restricted diet. They found that before beginning their diets, obese people, like obese mice, had fewer bacteroidetes and more firmicutes than lean control participants. During the dieting, the bacteroidetes became more abundant relative to firmicutes, regardless of whether the diet was low-fat or low-carb.

In a News & Views' article accompanying the papers, Matej Bajzer and Randy Seelye of the University of Cincinnati call the findings potentially revolutionary,' but also note that it is not clear whether such small changes in caloric extraction can actually contribute to meaningful differences in body weight. There are few data that substantiate the predicted increased caloric extraction in obese humans.'

Despite these caveats, Bajzer and Seelye agree with the conclusion of Gordon's team that obesity appears to have a microbial component and that this finding may have therapeutic implications. They write that the results tempt consideration of how we might manipulate the microbiotic environment to treat or prevent obesity.'

Dieting may have gotten rid of some of those firmicutes, but it has its own pitfalls: notably, rebound feeding, or the tendency to compensate for periods of food deprivation after they are over.

In the Cell paper, researchers From Yale University in New Haven, Conn.; Rockefeller University in New York City; Universite Laval in Quebec; Yunyang Medical College in Hubei, China; and the Universite Rene Descartes in Paris discuss how hunger is maintained during fasting, and the mechanisms of rebound feeding.

The researchers describe the interplay between the hypothalamic hormone triiodothyronine, or T3, and the protein uncoupling-protein 2 or UCP2, that is responsible for the feeling of hunger after reduced food intake.

The authors first demonstrated in anatomical studies that cells making the enzyme DII, which catalyzes the formation of T3, are next-door neighbors to those that produce UCP-2.

In mice that were food-deprived for 24 hours, the arcuate nucleus showed an increase in DII, which led to an increase in T3 and the activation of UCP2. That UCP2 activation resulted in the formation of mitochondria in the hypothalamic neurons, and it was the mitochondria were responsible for rebound feeding by the animals following food deprivation. Animals lacking either UCP2 or the DII showed reduced rebound feeding after the 24-hour fast.