That said, fructose has also been implicated in non-caloric metabolic effects including promoting insulin resistance and systemic inflammation.
Now a study by Jessica Kuzma and colleagues from the┬áFred Hutchinson Cancer Research Center, Seattle, WA, published in the American Journal of Clinical Nutrition, specifically addresses the hypothesis that fructose-sweetened beverages can promote systemic inflammation.
For their study, they randomised 24 otherwise healthy participants to three 8 day┬áperiods during which participants consumed┬á4 daily servings of fructose-, glucose-, or HFCS-sweetened beverages accounting for 25% of estimated calorie requirements while consuming a standardized diet ad libitum.
During the study┬ásubjects consumed 116% of their estimated calorie requirement while drinking the beverages with no difference in total energy intake or body weight.
Neither fasting plasma concentrations of C-reactive protein or┬áIL-6 changed during the study.
Furthermore, there were no consistent changes in measures of adipose tissue inflammation or in intestinal permeability.
Overall, the researchers conclude that consuming an excessive amount of fructose, HFCS, and glucose derived from SSBs consumed, at least in the short term (8 days), does not appear to promote systemic inflammation in otherwise healthy┬áadults.
Obviously, this study does not address the issue of wether or not overconsumption of sugar-sweetened┬ábeverages can promote obesity or whether cutting out such beverages has any other advantages short of lowering caloric consumption.
However, there is also new data suggesting that altered immune function may well be an important causal step in the accumulation of excess fat and related metabolic abnormalities.
Two studies, both in animal models, point to a role of perforin, a┬ácytotoxic effector molecule primarily released by CD8+┬áT cells and natural killer (NK) cells to eliminate infected or dangerous cells via the perforin-granzyme cell death pathway. In rare cases of humans with┬áimpaired perforin-dependent cytotoxic function, one often sees excessive T-cell activation, severe hyper-inflammation and possibly death.
The first study by Xavier Revelo and colleagues from the University of Toronto, published in Diabetes,┬áperforin-deficient mice (Prf1null), which show early increased body weight and adiposity, glucose intolerance, and insulin resistance when placed on high-fat diet (HFD) were shown to have an increased accumulation of proinflammatory IFN-╬│ÔÇôproducing CD4+┬áand CD8+┬áT cells and M1-polarized macrophages in visceral adipose tissue.
Furthermore, transfer of CD8+┬áT cells from┬áPrf1null┬ámice into CD8-deficient mice (CD8null) resulted in worsening of metabolic parameters compared with wild-type donors, thus demonstrating a role for T-cell function in insulin resistance associated with visceral adipose tissue.
In a second independent study by Yael┬áZlotnikov-Klionsky and colleagues from the┬áWeizmann Institute of Science in Rehovot, Israel, published in Immunity, showed that animals selectively lacking perforin-rich granules in their dendritic cells,┬áprogressively gained weight and exhibited features of metabolic syndrome, an effect that could be completely prevented by T cell depletion.
Both studies show that the immunoregulatory protein perforin appears to be an important regulator or body weight and metabolic function – a finding, which may well open a new door biological drivers of obesity.
Incidentally, perforin also plays a role in auto-immune diseases and this finding may thus provide a link between the common occurrence of obesity in people with auto-immune disease and has led some authors to even suggest that obesity itself may be a form of auto-immune disease.
While the therapeutic options will certainly not be as simple as replacing low levels of perforin, understanding exactly how immune function ties into the regulation of body weight may eventually lead to novel targets.
This year’s prestigious Fredrich┬áWassermann┬áAward of the European Association for the Study of Obesity presented at the 22nd European Congress on Obesity goes to Helsinki’s Aila Rissanen, Europe’s grande dame of obesity research.
I have personally known Aila for as lo as I have been involved in obesity and there is much in her work and approach to obesity that has stimulated my own thoughts on this issue.
In her acceptance address, Aila chose to focus on her work in BMI-discordant twins (among the many topics she has worked on) due to the remarkable insights into the “natre-nurture” discussion that this model offers.
Indeed, it is extremely rare to find genetically identical twins, who differ in body weight (demonstarting just how highly heritable body weight actually is). Thus, body weight in identical twins is remarkably homogeneous not only because of the heritability of weight per se but also due to heritability of weight gain.
Cining the work of her wildly successful trainee Kirsi Pietilainen, Aila described the efforts it took to identify just 30 obesity discordant (weight difference of >10 Kg) identical twins from well over 500 identical twin pairs.
These discordant twin pairs have now been extensively phenotyped with every imaginable laboratory test, measurement and tissue biopsies.
The most consistent difference between the discordant twins appears to be a greater level of physical activity in the leaner twin, which appears to precede the onset of weight gain.┬á In addition to voluntary physical exertion, there also appears to be a significant difference in fidgeting between the twins.
Compared to their co-twins, the obese twins had greater pro-inflammatory lipid profiles, lower antioxident activity and higher pro-coagulation markers. The reasons for these differences remains unclear.
Finally, Aila provided a brief overview of some of the exciting work that is now going on to further study the differences between these genetically identical but obesity disparate twins – metabolomics, lipidomics, epigenomics and even bacteriomics.
Although any of this has yet to translate to better obesity prevention or management, you never know where these fundamental insights into human biology may lead you.
For know, this is certainly a space I intend to watch.
Prague, Czech Republic
With all of the recent interest in the gut microbiota as a mediator of systemic inflammation and metabolic disease, it was only a matter of time before researchers would begin targeting pro-inflammatory pathways in the gut to change metabolism.
A proof-of-principle, that this is indeed possible, is presented by Helen Luck and colleagues from the University of Toronto in a paper published in Cell Metabolism.
Using mice models, the researchers not only show that a high-fat diet can alter the┬águt immune system but also that the┬áchronic phenotypic pro-inflammatory shift in bowel lamina propria immune┬ácell┬ápopulations is reduced in genetically altered mice that lack beta7 integrin-deficient mice (Beta7null), a driver of gut inflammatory response.
Further more, treatment of high-fat-fed normal mice with the local gut anti-inflammatory agent 5-aminosalicyclic acid (5-ASA), reverses bowel inflammation and improves metabolic parameters including insulin resistance (although it had no effect on body weight).
These beneficial effects are are associated with reduced gut permeability and endotoxemia as well as decreased visceral adipose tissue inflammation.
Moreover, treatment with ASA also improved antigen-specific tolerance to luminal antigens.
Thus, as the authors conclude,
“…the mucosal immune system affects multiple pathways associated with systemic insulin resistance┬áand represents a┬ánovel therapeutic target in this disease.”
Clearly gut inflammation both in relationship to gut microbiota as well as response to dietary factors is likely to be a hot topic in obesity and metabolic research for the foreseeable future.
Now a study by Benoit Chassaing and colleagues published in NATURE, suggests that dietary emulsifiers may promote weight gain and the metabolic syndrome by altering the composition of intestinal microbes.
The researchers hypothesized that emulsifiers may increase bacterial translocation across intestinal mucosa, thereby promoting local and systemic inflammation as well as affecting the composition of gut bacteria.
Their study in mice show that relatively low concentrations of two commonly used emulsifiers (carboxymethylcellulose and polysorbate-80) can induce low-grade systemic inflammation, weight gain and features of the metabolic syndrome, as well as promote intestinal inflammation in mice susceptible to inflammatory bowel disease.
Importantly, they used germ-free mice and faecal transplants to show that these changes can be induced simply by transferring the gut microbes from emulsifier-treated animals to controls.
As the authors note,
“These results support the emerging concept that perturbed host-microbiota interactions resulting in low-grade inflammation can promote adiposity and its associated metabolic effects. Moreover, they suggest that the broad use of emulsifying agents might be contributing to an increased societal incidence of obesity/metabolic syndrome and other chronic inflammatory diseases.”
While these findings (if replicated in humans) certainly point to the industrial use of food emulsifiers as a potential cause of the global increase in obesity and inflammatory bowel disease, given that these compounds are present in virtually all processed foods, they may well be difficult to avoid.
Guess it’s back to home cooking with raw ingredients.