Can Viruses Cause Obesity?

Is it possible that viruses can cause obesity? I'm not talking here about what we consider common viruses like the cold virus or HIV virus that attack humans directly, but bacteriophages, which attack bacteria and can kill them.

In fact, some people are using bacteriophages, often called just phages, to treat antibiotic-resistant bacterial infections. Phages were discovered in 1915 by FW Twort in England and then in 1917 by the Canadian Félix d’Herelle but haven't been studied a lot since then in terms of human disease.

Now there is some evidence that phages in the gut can contribute to obesity.

The idea that the gut microbiome can contribute to obesity is not new. Numerous studies have shown that transferring a sample of gut bacteria from fat animals into the guts of animals raised in sterile environments will produce fat animals, and transferring bacteria from thin animals will produce thin animals.

So it was not a surprise when University of Iowa scientists showed that the weight gain that often results from use of the drug risperidone, used for psychiatric disorders, was related to the gut microbiome of mice. What is interesting is that the researchers were able to cause the weight gain not just by transferring samples of the gut microbiota, but also by transferring the gut phages alone. When they gave the mice samples of isolated phages, the mice had decreased energy expenditure and a significant increase in weight, just as they had with the drug risperidone.

The usual caveat applies. Humans don't always react like mice. For one thing, humans don't set up  housekeeping in my walls. But our physiology is also somewhat different.

Nevertheless, the idea that bacteriophages could be affecting our weight is intriguing, and further research could lead to new approaches to keeping us all thin.

Spinning the News

I recently posted a blogpost about how the popular press often simply regurgitates press releases publicity people at various institutions send them.

And now come two "stories" that are such blatant attempts to trump up business for a certain food -- pears -- that it's laughable. One says pear consumers weigh less than non-pear-eaters, and the other says pears are healthy.

One study was sponsored by USA Pears, the other by the Pear Bureau Northwest, which is, in their words, "a nonprofit marketing organization to promote the fresh pears grown in Oregon and Washington."

Then one paper says, and this is the shocking part, "While the body of evidence connecting pear intake and health outcomes is still limited, USA Pears has been contributing to research efforts by commissioning independent studies to learn and affirm the heath attributes of pears."

Hold on! USA Pears has commissioned research aimed at proving that pears are healthy? Presumably if the research shows that pears cause warts, they won't publish that. But that's not scientific research. Scientific research tries to ascertain the truth, not support some preconceived conclusion. So OK, in fact this ideal is often not reached. But at least you should pretend you have an open mind.

The other study concludes that "intervention studies with pears that show positive health outcomes, most likely improvements in gut health, are urgently needed." In other words, research that shows negative outcomes is not needed.

What bothers me is that this kind of "research" and the ensuing press releases do, in fact, work. Most people seeing headlines like this or hearing them read out on the evening news will only remember, "Gosh. Pears are healthy and if I eat pears I'll lose weight." In fact, when you don't have diabetes, most fruits are healthy in moderation. Each fruit is higher or lower in some nutrient, but they all contain healthy nutrients as well as sugars.

I keep those 100-calorie sugarfree canned fruits on hand to use when my blood glucose goes too low, and they do a good job of raising my blood glucose and taste good as well. But I don't expect to be a lot healthier or to weigh less as a result.

At this point, except for occasional rants like this one, whenever I see a story promoting the health benefits of a single food, I look to see who funded the study. If it's some growers' organization like USA Pears, I don't even bother reading the story. There's enough real science research to read about without wasting time on this sort of thing.

Is There a Type 4 Diabetes?

A new type of diabetes in older people of normal weight has been proposed, and the authors suggest calling it type 4 diabetes. Well, OK, this hasn't been found in people yet, but only in mice, and mouse results often don't translated into human results, but the idea is intriguing.

The two main types of diabetes currently accepted are type 1, which is autoimmune, and type 2, which is caused by insulin resistance. Some type 1 patients have some insulin resistance and some type 2 patients have some autoantibodies, but in general types 1 and 2 have different causes.

Type 3 diabetes is what some people call Alzheimer's disease, meaning insulin resistance in the brain. Others use type 3 to mean family members of someone who has diabetes, some use it to refer to gestational diabetes, and some use type 3 to mean people whose diabetes is related to exposure to electromagnetic radiation. Definitions of type 1.5 diabetes also differ. Some use it to mean LADA (latent autoimmune diabetes of adults), which is like type 1 in older people but tends to progress more slowly. Others use it to mean people with both types 1 and 2, or "double diabetes." 

Another type of diabetes is MODY, or maturity onset diabetes of the young, which is monogenic. There are several types of MODY.

So now we may have another type of diabetes, which seems to be found in lean elderly mice in which  insulin resistance is caused not by obesity but simply by aging. The interesting thing is that this type of diabetes doesn't respond to weight loss but can be treated, at least in mice, by using antibodies to deplete the fat cells of immune cells called regulatory T cells, or Tregs. The Tregs in fat are called fTregs.

What is interesting about the Tregs is that they have been considered "good" immune cells. The Tregs control the immune system and can dampen down an immune response that is too large. There is some evidence that people with type 1 diabetes don't have enough Tregs so their immune system goes into overdrive and attacks their own tissues, including the beta cells in the pancreas.

One recent study showed that removing cells producing Tregs from people with type 1 diabetes,  culturing them in medium until they increased 1,500 fold, and then reintroducing them back into the patients produced no side effects. It is hoped that further trials show that they dampen the autoimmune attack.

But in the case of type 4 diabetes, the problem is not too few Tregs but too many in the fat cells, the fTregs. When the Salk Institute researchers, led by Ronald Evans, looked at the fTregs of obese mice with type 2 diabetes, they found that the level was lower than normal. But when they looked at the fTregs of aged lean mice with age-associated insulin resistance, they found that the levels were high (5%, compared with 0.4% in  young mice and 0.1% in obese mice). Their publication in Nature is behind a paywall, but Evans kindly sent me a copy of the full text.

When they depleted the fat of the excess fTregs by giving them a specific antibody, their metabolic abnormalities improved, glucose and insulin levels were lower, their fat cells were smaller, their serum free fatty levels were reduced to almost half of their previous levels, and they were leaner despite increased food consumption. Giving the same antibody to mice with type 2 diabetes had no effect.

As noted, this research has not yet been duplicated in humans. But the idea is exciting, because many older people diagnosed with type 2 diabetes find that weight loss has no effect. Others are diagnosed with type 2 even though they are active and of normal weight. If type 4 diabetes turns out to exist in humans, this would explain these anomalies.

Stay tuned. Evans said the research has generated a lot of interest, and I hope it's followed up in several labs, which offers the greatest possibility of confirmation.

Glucagon Again

I've written before about glucagon (here and here) and  have suggested that we need more research on alpha cells and glucagon, which sometimes seem to be ignored. Robert Unger has been writing about this for decades, but most researchers continue to focus on insulin.

In general, glucagon does the opposite of insulin. Insulin is produced by the beta cells in the pancreas and makes blood glucose (BG) levels go down. Glucagon is produced in the alpha cells in the pancreas and makes them go up. It's the ratio of the two that is important.

And now comes research showing that certain versions of the TCF7L2 gene, which are known to increase the risk of type 2 diabetes and were thought to work by inhibiting the secretion of insulin by the beta cells, may also work by making the alpha cells resistant to the action of insulin, which normally shuts them off. The senior author of the paper, Adrian Vella, kindly sent me the full text of the article.

When everything is working correctly, you eat carbohydrate and your beta cells produce and secrete insulin, which helps muscle and fat cells take up glucose. The insulin also turns down the secretion of glucagon by the alpha cells, which makes sense. Glucagon makes the liver produce and release a lot of glucose, and that's not something you want when your BG levels are already high.

The problem is that when you have type 2 diabetes, not only are your insulin levels too low to overcome your insulin resistance, but your glucagon levels are too high. And for those with the high-risk version (TT) of the TCF7L2 gene (and I have the protective version, CC, according to 23&Me), one reason for this high glucagon level seems to be that the insulin doesn't turn down its production in the alpha cells. So even when you eat carbohydrate and have enough insulin, the liver keeps pouring out glucose.

The study also showed a slight decrease in insulin production in those with the high-risk version of the gene, but no difference in the effectiveness of the insulin that was produced.

The differences in glucagon levels in those with the high-risk version of the TCF7L2 gene were not enormous. Clearly, the high-risk version of the gene is not the only contributor to type 2 diabetes. But that is consistent with the idea that type 2 diabetes is caused by small effects from many genes and not just one gene, as occurs in MODY, or maturity onset diabetes of the young. That's one reason why there's so much variation in the way we respond to various factors. I may have a defect in a different gene or genes than you do.
 But this research is a reminder that alpha cells and glucagon are important contributors to the type 2 diabetes puzzle,  and genetic and environmental effects on alpha cells may turn out to be as important as the effects on beta cells. "It demonstrates a completely novel mechanism of predisposition to diabetes that could lead to novel therapies," said Vella.