Seminar: GDF15 in regulation of food intake and metabolism v/ Sebastian Beck Jørgensen

August Krogh Club Seminar

GDF15 in regulation of food intake and metabolism

v/ Sebastian Beck Jørgensen, Principal Scientist, Global Obesity Research, Novo Nordisk, Denmark. 

Abstract

Growth differentiation factor 15 (GDF15; also known as MIC-1) is a divergent member of the TGF-β superfamily and is associated with body-weight regulation in humans and rodents. However, the cognate receptor of GDF15 is unknown.

Here we show that GDF15 binds specifically to GDNF family receptor α-like (GFRAL) with high affinity, and that GFRAL requires association with the coreceptor RET to elicit intracellular signaling in response to GDF15 stimulation.

We also found that GDF15-mediated reductions in food intake and body weight of mice with obesity were abolished in GFRAL-knockout mice.

We further found that GFRAL expression was limited to hindbrain neurons and not present in peripheral tissues, which suggests that GDF15-GFRAL-mediated regulation of food intake is by a central mechanism. Lastly, given that GDF15 did not increase energy expenditure in treated mice with obesity, the anti-obesity actions of the cytokine are likely driven primarily by a reduction in food intake.

Literature

Associating GDF15/MIC-1 with appetite regulation

Discovery of the GDF15/MIC-1 receptor

Regulations of GDF15

Time

6 September 2019

14:00-15:00: Seminar and discussion
15:00-16:00: Post seminar servings and socializing

Venue

Auditorium 1, August Krogh Building, Universitetsparken 13, DK-2100 Copenhagen

Registration

Participation is free, but please register here.

For PhD students

PhD students participating in August Krogh seminars receive 0,2 ECTS per seminar

Contact

Jonas Møller Kristensen, jmkristensen@nexs.ku.dk 

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