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Immune cells tweak the body
Obesity has reached epic proportions in the United States and is rising in other developed and developing countries as they adopt our diet and lifestyle. Autoimmune diseases, like celiac disease and multiple sclerosis, and allergies, also immune-mediated, have blossomed recently, too.
These conditions have exploded within too short of a time period to be attributable to genetic changes, so environmental factors, from synthetic pesticides to plastics to antibiotics, have been blamed for their increased prevalence. While it's probably simplistic to search for one cause to explain away both these types of modern ills, some studies are indicating that immune cells and molecules are important for regulating metabolism—and are dysregulated in obesity.
A specific type of immune cells, called Group 2 innate lymphoid cells (ILC2s), were found in white adipose tissue in mice last year. Now, they have been found in the same tissue in humans. Obese people, along with obese mice, have fewer of these cells in their fat than lean individuals do.
These cells respond to an immune signaling molecule called interleukin 33 (IL-33); that same molecule diminishes obesity by increasing caloric expenditure. This increased caloric expenditure is not due to increased physical activity or to burning more calories as more food is consumed. Instead, IL-33 just enhances the number of calories burned by normal physiological processes. Researchers figured all of this out by playing with mice deficient in IL-33 as well as those deficient in ILC2s—feeding them high fat versus regular chow, treating them with injections of IL-33, and comparing them to normal mice.
So, how does the fact that ILC2s are present in fat cells come into this? Fat is available in a number of boring neutral colors. White adipocytes store energy as large fat droplets. Brown adipocytes have much smaller lipid droplets and specialize in burning them, yielding heat; they are brown because they contain many mitochondria, which have iron in them. By converting fat to heat, brown fat cells help limit obesity. As its name indicates, the newly recognized beige fat is an intermediate between them. Beige adipocytes, like the brown ones, also produce heat and might protect against obesity.
Using the same genetically engineered mice described above, the researchers found that "IL-33 may be a critical regulator of beiging"—it helps convert white adipocytes into beige ones. And it needs ILC2s to do so.
So, in addition to their expected immune duties like responding to tissue damage and inflammation, ILC2 cells can help turn white fat cells into beige ones in both mice and men. Coupling immune and metabolic regulation into one cell type may have been useful evolutionarily in helping mammals deal with environmental stresses like infections, times of nutritional scarcity, and climate changes.
Since the beiging process limits obesity by enhancing caloric expenditure, ILC2s and IL33 may provide druggable targets to treat obesity and all of its associated diseases.
Obesity has reached epic proportions in the United States and is rising in other developed and developing countries as they adopt our diet and lifestyle. Autoimmune diseases, like celiac disease and multiple sclerosis, and allergies, also immune-mediated, have blossomed recently, too.
These conditions have exploded within too short of a time period to be attributable to genetic changes, so environmental factors, from synthetic pesticides to plastics to antibiotics, have been blamed for their increased prevalence. While it's probably simplistic to search for one cause to explain away both these types of modern ills, some studies are indicating that immune cells and molecules are important for regulating metabolism—and are dysregulated in obesity.
A specific type of immune cells, called Group 2 innate lymphoid cells (ILC2s), were found in white adipose tissue in mice last year. Now, they have been found in the same tissue in humans. Obese people, along with obese mice, have fewer of these cells in their fat than lean individuals do.
These cells respond to an immune signaling molecule called interleukin 33 (IL-33); that same molecule diminishes obesity by increasing caloric expenditure. This increased caloric expenditure is not due to increased physical activity or to burning more calories as more food is consumed. Instead, IL-33 just enhances the number of calories burned by normal physiological processes. Researchers figured all of this out by playing with mice deficient in IL-33 as well as those deficient in ILC2s—feeding them high fat versus regular chow, treating them with injections of IL-33, and comparing them to normal mice.
So, how does the fact that ILC2s are present in fat cells come into this? Fat is available in a number of boring neutral colors. White adipocytes store energy as large fat droplets. Brown adipocytes have much smaller lipid droplets and specialize in burning them, yielding heat; they are brown because they contain many mitochondria, which have iron in them. By converting fat to heat, brown fat cells help limit obesity. As its name indicates, the newly recognized beige fat is an intermediate between them. Beige adipocytes, like the brown ones, also produce heat and might protect against obesity.
Using the same genetically engineered mice described above, the researchers found that "IL-33 may be a critical regulator of beiging"—it helps convert white adipocytes into beige ones. And it needs ILC2s to do so.
So, in addition to their expected immune duties like responding to tissue damage and inflammation, ILC2 cells can help turn white fat cells into beige ones in both mice and men. Coupling immune and metabolic regulation into one cell type may have been useful evolutionarily in helping mammals deal with environmental stresses like infections, times of nutritional scarcity, and climate changes.
Since the beiging process limits obesity by enhancing caloric expenditure, ILC2s and IL33 may provide druggable targets to treat obesity and all of its associated diseases.