During fasting our body needs additional sources of energy and that's why triglycerides are broken down into fatty acids and glycerol. where fatty acids can be used to generate acetyl-coA and contribute to the citric acid cycle or build ketone bodies.

So if we are wishing to get more fatty acids why is LPL down-regulated although it's the enzyme needed to break down Triglycerides in lipoproteins?

  • $\begingroup$ Please provide a reference or link to your assertion that LPL is down-regulated. See "how do I ask a good question" in the Help. In particular it is imperative to state what tissue(s) you are referring to. $\endgroup$ – David Mar 25 '18 at 19:27
  • $\begingroup$ An edit was requested, and I have updated the answer below. Let me know if there is any confusion. $\endgroup$ – CKM Mar 26 '18 at 0:54

LPL is largely expressed on tissues that metabolize or store a lot of fat, including muscle and adipose tissue, and it's regulated by a number of factors (1). This includes diet, hormones and other protein regulators. The current literature on LPL has shown that regulation of LPL is tissue-specific. The activity of LPL, like other proteins, may be controlled at the transcriptional or the post-transcriptional level. A review by Goldberg et al (2009) notes that the activity of LPL in adipose tissue during fasting is low, but high in skeletal and cardiac muscle. They also note that insulin increases transcription of LPL in adipose. So why the down-regulation? One of the proposed mechanisms for LPL down-regulation in adipose tissue is rapid inactivation by a protein inhibitor known as ANGPTL-4 (2)

ANGPTL-4 (also known as a fasting-induced adipose factor), is up-regulated in adipose tissue two to four-fold in response to glucocorticoid stimulation (3). It's commonly known that you have a cortisol spike within a few hours of fasting, which is intended to try and increase glucose availability, for example.

The idea is that ANGPTL-4 attempts to control the distribution of fatty acids (4). In a mouse study, Cushing et al. demonstrated that ANGPTL-4 in fact diverts uptake of fatty acids and triglycerides away from adipose tissues (5). And this study was published in August 2017, so the phenomenon is still under investigation. It makes sense though, right? Why does the adipose tissue need to continue to receive fats during fasting? They can be better served elsewhere like muscle, the brain or the liver. Not only so, but Catoire et al. also demonstrated in 2014 how the interplay between ANGPTL-4 and LPL between non-exercising and active skeletal muscle during exercise allows for fine-tuning of fatty acid delivery to sites that need it most (6). So the regulation extends to both inter- and intra-tissue needs.

In closing, LPL is regulated during fasting in a targeted manner, but it is not generally down-regulated. Regulation is controlled in a manner that allows the demands of tissues to be reactive to their environment.

  • $\begingroup$ I'm sorry but I do not understand your answer. I can understand why the skeletal muscle is regulated differently than adipose tissue, but Is LPL down-regulated in adipose tissue during fasting and if so why? If not, please say so. And you may know a lot about it but do you really have to bring ANGPTL-4 into this? $\endgroup$ – David Mar 25 '18 at 19:34
  • $\begingroup$ @David LPL is not generally down-regulated during fasting. One of the take-home points that I may not have communicated properly is that LPL is regulated at the tissue level. Adipose LPL activity is low during fasting, but high in muscle. The proposed mechanism for rapid adipose LPL inactivation is the up-regulation of ANGPTL-4 in that tissue. I will edit the answer. $\endgroup$ – CKM Mar 26 '18 at 0:41
  • $\begingroup$ Furthermore, I wanted to make note using ANGPTL-4 as an example that it wasn't a fat vs. muscle dichotomy, and that LPL may be regulated within a single type of tissue, as well. $\endgroup$ – CKM Mar 26 '18 at 0:51

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