After every meal, the body must prevent the immune system from launching an all-out fight against food. Now, researchers report the identity of a nutrient "floodgate" that serves to protect against such an inflammatory immune response.
The researchers found that animals lacking a protein enriched in fat cells, called STAMP2, develop acute inflammation in deep pockets of visceral fat. The animals also showed symptoms of metabolic syndrome—including insulin resistance and fatty liver disease—even while eating a regular diet.
In those who regularly consume an overload of nutrients, the flood control protein may become overwhelmed and give out, leading to the chronic, low-grade inflammation characteristic of obesity and other metabolic diseases, the researchers suggest. Treatments designed to reinforce that barrier may therefore provide the "next frontier" of therapies to combat the rising tide of chronic metabolic disease, they said.
"Humans were not meant to deal with little to no exercise and a constant bombardment of nutrients," said Gökhan Hotamisligil of the Harvard School of Public Health of his team’s findings. "If we could find ways to strengthen STAMP2 or prevent its suppression, the body might retain control," effectively unlinking chronic overeating and obesity from other symptoms of metabolic disease. He cautioned, however, that the realization of such a treatment strategy remains uncertain and would require years of continued investigation.
Cells and organisms must strike an appropriate balance between nutrient sufficiency and surplus, the researchers explained. While adequate amounts of nutrients must be obtained to ensure health and survival, chronic overeating can lead to obesity and an array of associated metabolic disorders, including insulin resistance, fatty liver disease, type 2 diabetes, and cardiovascular disease. This cluster of chronic diseases now constitutes the largest global health threat, Hotamisligil said.
Their current findings pinpoint STAMP2 as a critical factor to prevent overt inflammatory responses during everyday nutrient fluctuations or conditions of nutrient excess. In fat cells, a lack of STAMP2 led to aberrant inflammatory responses to both nutrients and acute inflammatory stimuli, they reported.
Similarly, they showed that the visceral fat surrounding the internal organs of STAMP2-deficient mice became inflamed, and the animals developed spontaneous metabolic disease on a regular diet, manifesting insulin resistance, glucose intolerance, high blood sugar and lipid levels, and fatty liver disease. They also showed that the loss of STAMP2 exacerbated the metabolic symptoms of mice with a genetic predisposition to obesity due to other factors.
When food enters the system, STAMP2 normally keeps the immunity response "button" from getting pushed, Hotamisligil said.
"We suggest that, over time, the accumulation of small cellular stresses due to daily changes and fluctuations in nutrients in STAMP2-deficient mice may lead to the activation of inflammatory pathways and inhibition of insulin action, resulting in systemic metabolic deterioration over the long term," he continued.
Source: Cell Press.
- PHYSICAL SCIENCES
- EARTH SCIENCES
- LIFE SCIENCES
- SOCIAL SCIENCES
Subscribe to the newsletter
Stay in touch with the scientific world!
Know Science And Want To Write?
- On Sexuality, You Weren't Born That Way, Says Paper
- Bubble-wrapped Sponge Creates Steam Using Sunlight
- Reframing Body Weight As Baby Weight May Help Women Handle Pregnancy
- Petition: Let's End Dramatized Reporting Of "Doomsday" Stories - The Vulnerable Get Suicidal
- Watching Thoughts -- And Addiction -- Form In The Brain
- Post-Doctoral Positions In Experimental Physics For Foreigners
- Stem Cell Therapy Heals Injured Mouse Brain
- "i've often wondered https://en.wikipedia.org/wiki/Behavioral_sink ..."
- "Dylan, yes back online now. The Sun, and Moon are visible in all those places, of course, so if..."
- "Tina, I think it's best to try to understand the constellation argument because then you can just..."
- "People worry about a system entering ours and spelling doomsday for us all, however I believe if..."
- " I appreciate your hard work and look forward to any future publications with great interest, thank..."
- Fauci: Don’t Make Policy Based on Animal Studies
- Exercise Could Save Your Liver
- Precision Medicine Stands On Imprecise Infrastructure
- Standing with Giants: A Collection of Public Health Essays in Memoriam to Dr. Elizabeth M. Whelan
- RIP Dr. D.A. Henderson, ACSH Trustee Who Helped End Smallpox
- How Safe Are Tattoos?
- Study uses geo-mapping to identify 'hot spots' for use of fentanyl and other opiates
- Study examines families' journeys to accepting transgender children
- Private detention of immigrants deters family visits, study finds
- Study finds changes to retirement savings system may exacerbate economic inequality
- Traumatic brain injury associated with long-term psychosocial outcomes