GDF15: Monkeys And Mice Gift Humans With Stressful Weight Loss

Mice, Monkeys, and also Rats have given their lab-tested time and stress to a set of researchers searching for weight loss. What they found was a protein by the name of Growth Differentiation Factor-15, AKA GDF15 (also known as MIC-1). This protein was discovered by researchers from three different pharmaceutical companies and published in three papers, each independent of the other – that doesn't sound suspicious to you, does it?

The first person to note the potential for GDF15's potential for weight-loss was Samuel Breit, an physician and immunologist at St. Vincent's Hospital in Sydney, Australia. Breit was part of a group of researchers to publish a paper about GDF15 in the year 2011. That paper went by the name "The TGF-β superfamily cytokine, MIC-1/GDF15: A pleotrophic cytokine with roles in inflammation, cancer and metabolism" and can be found at T&FOnline.

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In that paper, Breit (et. all) suggest the connection between appetite suppression and GDF15. "Furthermore, in late-stage cancer, large amounts of MIC-1/GDF15 in the circulation suppress appetite and mediate cancer anorexia/cachexia, which can be reversed by monoclonal antibodies in animals." Breit's research showed how GDF15 more than likely acted through the brain.

In August, a paper was published by Linda Yang et. all in Nature with the title "GFRAL is the receptor for GDF15 and is required for the anti-obesity effects of the ligand." In the paper, Linda and crew suggest the following: "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."

Once researchers had a target, they found this "GFRAL" in two regions of a mouse brain. The mouse had its GFRAL gene turned on, and GFRAL appeared in the postrema and the nucleus of the solitary tract. The first of these two regions is the vomit-inducing center, while the other is home to neurons that associate with appetite regulation (amongst others).

Both of these areas where GFRAL appeared were outside of the brain's blood-brain barrier. This means they've got real potential as targets for drugs – and not drugs that'd need to be jammed in to a person's skull with a monster needle. The only negative effect so far MIGHT be nausea – and since this is all closely related to stress-induced behavior, that's another real danger to the end user.

But apparently rats and mice and monkeys aren't all that good at telling researchers when they feel like throwing up or when they feel super stressed. So there's not really a good way to know how that bit will go down until human trials begin. It is quite likely that human trials will begin with a modified version of what's been tested on mice, rats, and monkeys – one slightly more targeted, and likely longer lasting.

For more information on this futuristic bit of research, have a peek at the paper "Non-homeostatic body weight regulation through a brainstem-restricted receptor for GDF15" in Nature as of this week. This paper is one of several (others linked above) that've come to similar conclusions about GDF15 in recent months. This paper was written by Jer-Yuan Hsu et al, and can be found under code doi:10.1038/nature24042 right this minute.

Also available on this subject is the paper "Obesity: Receptors identified for a weight regulator", also available in Nature as of this week. This bit of research was authored by Mart Saarma and Adrian Goldman and can be found with code doi:10.1038/nature24143 at the time this article is scheduled to be published.