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The Domingos lab has published a new opinion piece in Science investigating the implications of a Memorial Sloan Kettering Cancer Center study that lays the foundations for a potential new anti-obesity treatment in the form of targeting adipose tissue-resident macrophages.

Adipose tissue-resident macrophages control lipid storage through production of platelet-derived growth
factor (PDGFcc), which induces lipid retention in white adipose tissue adipocytes in a paracrine manner,
although the precise mechanism is unclear. Recruited macrophages are responsible for the inammation
that characterizes obese adipose tissue. Treatment with PDGFcc antibodies restores homeostasis, and
reduces lipid storage and body weight, redirecting excess lipids mostly to thermogenesis. © Science

Immune cells called adipose tissue-resident macrophages control how much fat is stored in the body by secreting a factor that promotes energy storage in adipocytes, also known as fat cells. A new article from Associate Professor Ana Domingos and BHF Cardiovascular Science DPhil Student Conan O’Brien reviews a new study that attempted to prevent promotion of fat storage. In doing so, they present evidence that an anti-obesity immunotherapy has been identified for the first time.

The study, conducted by Dr Nehemiah Cox and Professor Frederic Geissmann at the Memorial Sloan Kettering Cancer Center in New York, showed that an antibody treatment can inhibit the process of storing fat and cause a reduction in body weight, without affecting food intake. The antibody targets a protein called platelet-derived growth factor c, which is secreted by adipose tissue-resident macrophages. The antibodies bind to the protein and inhibit it from promoting fat storage in adipocytes.

According to O’Brien: “This study introduces a new, macrophage-centred paradigm in energy storage and provides proof of concept for an anti-obesity immunotherapy. It is still unclear the extent to which this finding will be translatable to humans, though single cell RNA sequencing of human adipose tissues tells us that human adipose macrophages also express platelet-derived growth factor c, so we could envision the mechanism being conserved and being a clinically relevant target in the future.”

The full article is available to read in Science: "An anti-obesity immunotherapy?"

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