A high-fat diet limits the brain’s ability to regulate food intake

Eating too much fat can cause the region of the brain that regulates food intake to malfunction, according to new research published in the journal Cell Metabolism.

Consuming too much fat is known to cause immune cells called microglia (which make up between ten and fifteen per cent of the brain) to expand in number and to trigger local inflammation within the mediobasal hypothalamus, which contains key groups of neurons that regulate food intake and energy expenditure.

During the study, mice were fed a diet rich in fat for four weeks. To establish that the multiplying microglia caused overeating and obesity, the researchers depleted the number of microglia in the brains of mice on the fatty diet by giving them an experimental drug called PLX5622.

They found that mice treated with the drug ate 15 per cent less and gained 20 per cent less weight than untreated mice on the same diet.

They also genetically engineered mice to prevent microglia from activating inflammatory responses, and found that these mice ate 15 per cent less and gained 40 per cent less weight on a high fat diet, suggesting that the inflammatory capacity of microglia itself is responsible for overeating and weight gain.

Joshua Thaler, the study’s co-senior author, said: ‘From these experiments we can confidently say that the inflammatory activation of microglia is not only necessary for high-fat diets to induce obesity, but also sufficient on its own to drive the hypothalamus to alter its regulation of energy balance, leading to excess weight gain.’


  • Tarek

    What kind of fat?Monounsaturated, polyunsaturated,saturated?Fat from natural sources or synthetic?What was the composition of the rest of the diet?Refined or natural carbohydrates?Are mice physiologically designed to naturally eat such a high fat diet or were the findings merely the result of disordered physiology as a response to an unnatural intake for the species?

    • AlexB

      Hush, Tarek. Can’t have you asking sensible questions.

  • AlexB

    I’m getting a “page not found” error on the link.

  • C. Richards Golini

    Saturated….if I understood correctly.