So after my rather harsh take on the last review paper you might beg the question: What does a good review article look like?

Well, I have to say that this article is an amazingly well written comprehensive review of the many various research aspects people are undertaking on lipases. Lipases are the catabolic enzymes that mediate lipolysis – the hydrolysis of fatty acids. In other words, lipases take the inert fat we store and break it up into fatty acids for our body to use as energy (and for other things like signaling, membrane lipids, etc).

Lipolysis requires 3 different consecutive steps that involve at least three different lipases: ATGL (the first, converting tricylglycerols into diacylglycerols), HSL (the second, converting diacylglycerols into monoacylglycerols), and MGL (the third, hydrolyzes MGs).

Before I continue, a quick warning: This review of lipase research is incredibly comprehensive and covers all recent research aspects of lipase including many that came out with conflicting or unclear results. Because this is my journal review, I am merely going to focus on the aspects I found most intriguing and/or had the best evidence presented. For all the nitty gritty, please do yourself a favor and read it yourself. Also I’m going to skip over hepatic aspects, but if you’re interested in fat storage in the liver, this subject is also covered in great detail. Now, back to lipases…

Of the AGTL, HSL and MGL lipase trio, ATGL is the newest enzyme found. Expression and regulation of this enzyme is complex. The mRNA expression of this enzyme is elevated by PPAR agonists, glucocorticoids, and fasting, whereas insulin and food intake decrease expression. (It seems to me insulin has its hands in so many pots, which may be why people who lower their insulin expression by undertaking a low carb diet often find such fantastic results.) mRNA does not necessarily mean there’s more enzymatic activity- however G0S2, a peptide inhibitor of ATGL, also is increased after feeding, and decreases during fasting.

ATGL has a coactivator protein that works as a super enhancer named CGI-58. This little guy often gets hogged up by perilipin-1, but under the right conditions when your friendly PKA comes around (hint: B-adrengeric stimulation), it will conveniently let go of CGI-58.

HSL is the next step in the chain. HSL is strongly induced by the B-adrenergic stimulation, wherease insulin has a strong inhibitory effect (there it is again!). HSL skips relying on second hand coactivators and the like, and likes to play with PKA itself. This makes our HSL a lot more effective at its job. I imagine being phosphorylated feels like how I feel after I get a couple good strong cups of coffee in me.

So let’s get down and dirty with insulin. Insulin-mediated deactivation of lipolysis seems to be associated with the downregulation of transcription of ATGL and HSL. Suddenly our fancy lipases aren’t being produced anymore. Insulin signaling also inhibits PKA, our friendly cup o’ joe. Insulin ALSO inhibits lipolysis by acting centrally via the sympathetic nervous system by inhibiting HSL and perilipin phosphorylation in white adipose tissue.

Well that was stressful. Let’s take it down a notch… Put on that Marley and get out that chronic. Yes I am making bad marijuana references right now. MGL is the final enzyme in this lovely cascade, and it leads a fascinating life. MG’s, as you remember, are what MGL munches down on to create usable fatty acids. However MG’s also have signaling potential: they act on cannabinoid receptors, thus affecting appetite, lipid metabolism, and energy homeostasis. Treatments on obese patients have suggested that they may struggle with an overactive endocannabinoid system, thereby promoting both appetite and lipid deposition. But interestingly enough, overexpression of MGL seems to promote the proliferation of tumor cells, which I believe may lead researchers to the obvious question of whether pot helps cancer patients in more than just pain relief. There may be a complicated feedback loop involved.

I believe the takeaway message from this review article is that insulin hates lipases, and there is a great deal of question and many unknowns in the complicated words of lipolysis. I look forward to the future research. We have currently just scratched the surface.

Resources

• FAT SIGNALS – Lipases and Lipolysis in Lipid Metabolism and Signaling, Zechner, Zimmerman et al. Cell metabolism doi:10.1016/j.cmet.2011.12.018 (volume 15 issue 3 pp.279 – 291)