Trypanosoma brucei (T. brucei) enters its host’s body through the painful bite of infected tsetse flies, causing sleeping sickness, which can be fatal if left untreated. In her laboratory at the University of Lisbon, parasitologist Luísa Figueiredo studies the mechanisms underlying T. brucei infections.

Her team previously found that T. brucei accumulates in large amounts in the adipose tissues of mice, where it undergoes changes in its ability to uptake and metabolize lipids.1 This observation, combined with the fact that Trypanosoma infections induce fat loss, led the team to hypothesize that the parasite alters lipid metabolism in adipose tissue.

          The photo shows a mixture of normal and atrophied adipocytes (white circles), T. brucei parasites (brown), and the nucleus of infiltrated immune cells (blue).
Adipose tissue serves as a reservoir for T. brucei parasites. The parasites (shown in brown) accumulate outside the adipocytes (white circles).
Tânia Carvalho

In their recent Nature Microbiology paper, the team reported that T. brucei stimulates lipolysis in fat cells by modulating the host enzyme that initiates this process. They also found that this response counterintuitively benefits the host, opening avenues for novel treatment strategies.

To uncover how the parasite induces fat loss, the researchers used wildtype and knockout mice that lacked adipocyte triglyceride lipase (ATGL), a key enzyme in lipolysis, in their adipose tissues. When infected with T. brucei, wildtype mice lost adipose tissue and had higher levels of fatty acids (FFA), a product of lipolysis. Despite preserving fat mass during the infection, ATGL-deficient mice had shorter lifespans and higher parasite loads in their fat tissues than their wildtype counterparts.

After identifying the FFA from the adipose tissues of wildtype mice and testing them on the parasite in vitro, the researchers were surprised to find that one fatty acid killed, rather than benefitted, the parasite.        

“It had often been thought that the wasting associated with these infections was a consequence of high parasitemia,” said Monica Mugnier, a T. brucei researcher at Johns Hopkins University who was not involved in the research. “This result shows that the fat loss may actually be a protective mechanism during the infection.”

References

  1. Trindade S, et al. Cell Host Microbe. 2016;19(6):837-848.
  2. Machado H, et al. Nat Microbiol. 2023;8(11):2020-2032.