Can Liraglutide Help Grow New Fat Cells?

The human GLP-1 analogue liraglutide is now approved for the long-term medical treatment of obesity in an ever-increasing number of countries. Its safety and clinical effectiveness is now well established and there is no doubt that this is an important addition to the rather limited number of treatment options available to people living with obesity.

Interestingly, however, liraglutide has also been shown to promote the differentiation of pre-adipocytes or, in other words, promote the formation of new fat cells.

While this may seen worrying or even counter-intuitive, we much remember that having more (smaller) rather than fewer (bigger) fat cells actually has substantial metabolic advantage s- there is indeed ample data showing that large adipocyte cell size and limited capacity to grow fat cells (the extreme case of which is seen in people with lipodystrophy) is actually a key risk factor for metabolic problems including insulin resistance, possible by promoting the accumulation of ectopic fat (e.g. in liver and skeletal muscle).

Now, a paper by Yongmei Liand colleagues, published in Molecular Medicine Reports provides additional insight into the cellular pathways involved in liraglutide’s adipogenic effects.

Using a series of in vitro experiments, the researchers show that liraglutide does indeed promote the adipogenic differentiation of 3T3-L1 cells (a widely used murine preadipocyte cell line)  through a process that upregulates the expression of C/EBPα and PPARγ at the early phase of adipogenic differentiation, promots the expression of lipogenesis associated genes including aP2, and enhances the accumulated of lipids.

At the same time, liraglutide appears to suppress cell proliferation via the Hippo‑yes‑associated protein (YAP) signaling pathway, thereby allowing these cells to transform into mature adipocytes sooner.

How relevant these observations are for humans remains to be seen, but certainly the promotion of adipogenic differentiation may hold the potential for improving insulin sensitivity and reducing the metabolic risks associated with excess weight gain.

@DrSharma
Edmonton, AB

Disclaimer: I have received speaking and consulting honoraria from Novo Nordisk, the maker of liraglutide.