Biology

Mice chow down on a high-fat diet without becoming fat

Mice chow down on a high-fat d...
After eight weeks on a high-fat diet, mice that had been engineered with genes to activate the Hedgehog signaling pathway didn’t gain weight (left), but control animals whose Hedgehog pathways were not activated became obese (right)
After eight weeks on a high-fat diet, mice that had been engineered with genes to activate the Hedgehog signaling pathway didn’t gain weight (left), but control animals whose Hedgehog pathways were not activated became obese (right)
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After eight weeks on a high-fat diet, mice that had been engineered with genes to activate the Hedgehog signaling pathway didn’t gain weight (left), but control animals whose Hedgehog pathways were not activated became obese (right)
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After eight weeks on a high-fat diet, mice that had been engineered with genes to activate the Hedgehog signaling pathway didn’t gain weight (left), but control animals whose Hedgehog pathways were not activated became obese (right)

Not getting fat or developing diabetes while still enjoying a high-fat diet is the dream of many a fast-food fan. Although such dreams remain just that for us humans, they've become reality for mice involved in a study at Washington University School of Medicine in St. Louis. The activation of a protein pathway in fat cells in the mice allowed the animals to be fed a high-fat diet without becoming obese.

The research conducted by a team led by senior investigator Fanxin Long, PhD focused on what's known as the Hedgehog signaling pathway. Not restricted to its spiny namesake, this signaling pathway, which is a key regulator of animal development, is present in all bilaterians (or animals that are bilaterally symmetrical – which is most animals, including humans). It has also been shown to play a role in inhibiting the development of adipose tissue, or fat.

To explore if Hedgehog signaling also has an effect on diet-induced obesity after birth, Long and his team genetically engineered mice so that the Hedgehog pathway in fat cells would activate when they ate a high-fat diet. Over an eight-week period, a control group of mice fed a high-fat diet predictably became obese, but the mice whose Hedgehog pathway had been activated didn't gain any more weight than another control group fed on a normal diet.

"More importantly, when we did metabolic studies, we found that the animals with the active Hedgehog pathway not only were leaner, they also had lower blood-glucose levels and were more sensitive to insulin," says Long.

Rather than preventing the mice developing more fat cells, keeping the weight off was due to the activation of the signaling pathway stopping the existing fat cells get bigger.

"Fat gain is due mainly to increased fat cell size," explains Long. "Each fat cell grows bigger so that it can hold larger fat droplets. We gain weight mainly because fat cells get bigger, as opposed to having more fat cells."

Long says it may be difficult to translate the findings to humans despite the belief that the pathway works in a similar way in mice and humans. This is due to malfunctioning of the Hedgehog pathway being linked to various diseases, such as basal cell carcinoma. So, the difficulty lies in targeting the pathway without causing unwanted side effects. However, Long is still hopeful the research could lead to a new therapeutic target to treat obesity.

"If we can come up with strategies to carefully target fat cells, then I think activating this pathway could be effective in the fight against obesity," he says.

The team's research is published in the journal eLife.

Source: Washington University School of Medicine in St. Louis

6 comments
IanWhiteley
Fat does not make you fat. Carbs and sugars make you fat. That is what is in excess in the "modern" diet.
Analyse any obese person's diet and you will note the general absence of fat, and an excessive indulgence in refined carbs and sugars (which supplement almost all "low fat" foods).
Asgard
This is basically a Ketogenic diet or Keto diet for short. It has become quite popular. I've been on and off it for about 6 months. It also keeps hunger pangs down between meals. When I go off it; it's because I've become bored with the somewhat limited foods to eat without going into a major production in cooking. A nice addition is something like a carrot and apple juice made from real carrots in a slow juicer so the good stuff doesn't get torn up in a fast juicer then adding some apple vinegar to it for an increase in digestive help. ($4 a gal at Walmart) Some say it helps with losing weight as well. About 8 oz with breakfast does it for me. The nice thing is carrots and a bag of any kind of apples isn't that expensive and you don't get all the added sugar or salt from the canned or bottled kind.
To lose weight simply don't have breakfast or anything else to eat until lunch 3 or more times a week. Wait till lunch and just have 2 main meals that day. Anyone will lose weight on this not really a diet diet. It's the breads, sugars, and extra sodium in pre-prepared processed foods that are the real problem in weight gain. I only wish I had discovered this simple solution at a much younger age.
Miner Bob
Ian is correct. I am living proof that fat does not make you fat. When I changed to a "Keto" diet of 90% fat and 10% protein with almost zero carbs and zero sugar, I lost 60lbs in 6 months with no changes in activity. I have clarity of thought, my blood sugar is normal, my LDL is normal and my Doctor is amazed. I am on zero meds now and have another 60 lbs to go and I love eating bacon every morning, butter coffee and steaks slathered in butter for dinner. NO cakes, cookies, chips, or sodas is small price to pay to be healthy.
Username
Ian, clearly, feeding fat to the control group made it overweight.
Mark Salamon
Username7 -- While it may be true that the control group of mice gained weight when fed a high-fat diet, human metabolism is not the same as mouse metabolism.
In humans, high carbohydrate intake, as well as diets high in BOTH carbohydrates and fat, will result in the accumulation of body fat.
However, human metabolism utilizes insulin to convert carbohydrates into body fat, while the fats we eat are used to produce energy. In general, people eating high-fat diets WITHOUT carbohydrates won't gain body fat.
toddzrx
I'll all the other comments about human intake of a high-fat, low carb or no carb diet: it works like a champ in terms of keeping weight off. If you don't think so, then try it. Run the experiment on yourself.