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Knocking out TLR4 in mice ameliorates obesity-associated inflammation, which may come as no surprise since increased circulation of LPS (a potent activator of TLR4) has been implicated in obesity due to associations with increased presence of LPS binding protein.
While genetically knocking out TLR4 is probably not a practical solution to the inflammatory cascade associated with human obesity, which may also be a smoking gun in obesity-associated brain shrinkage and diminished cognition, dietary intake of omega-3 fatty acids EPA and DHA may at least be partly ameliorative (see review). Additionally, a study in breast cancer patients showed that 5 grams per day of EPA and DHA ultimately lead to hypermethylation (usually interpreted as suppressive) of TLR4.
From the article:
When a person consumes more calories than needed, the excess calories are stored in the form of triglycerides inside fat tissue, also known as white adipose tissue (WAT). Researchers know that in obese people, WAT becomes overworked, fat cells begin to die, and immune cells become activated. But the exact mechanism by which this inflammation occurs isn’t fully understood.
After five months on a high-fat diet, the mice lacking Tlr4 had gained just as much weight, and just as much fat, as other mice on a high-fat diet. But the genetically engineered mice – with [fibro-inflammatory progenitors] that could no longer generate the same signals – no longer had high levels of inflammation. Instead, the levels of inflammatory molecules in their WAT were closer to the levels seen in mice on low-fat diets.