Tuesday, April 19, 2016

Palmitate In Vitro: Does Saturated Fat Impair the Circadian Rhythm?

A little while ago I wrote about a recent study that found a high fat diet induced weight gain and insulin resistance in mice – a thoroughly unsurprising result considering previous research and the mouse model used (blog).  Today I’m going to talk about another thoroughly unsurprising result, this time from a study that found palmitate (C16:0) is bad for cells – specifically shifting the circadian rhythm [1].  The study was reported in Science Daily, which reported that saturated fats 'jet lag' the body clocks, which triggers metabolic disorders [2]

The paper itself is quite lengthy, detailed and technical.  There’s a good chance the authors spent a fair bit of time on this.  In summary: palmitate alters the circadian rhythm, but DHA does not; and the effect of palmitate is probably due to inflammation [1].  The authors also cite similar results from other cell culture studies and results from mouse studies that found feeding them a high fat diet impairs their circadian rhythm

Palmitate (and LPS) are regularly used in cell culture studies to cause bad things to happen for your gene knockout/gene therapy/new drug/etc to protect against.  Below are a few studies I found following a brief search (just note that our study used 0.15-0.25 mM of palmitate or DHA [1]):

  • 0.5 mM palmitate (but not oleate) increases ceramide accumulation, the generation of reactive metabolites and apoptosis in CHO cells [3]
  • 0.1 mM palmitate impairs insulin signalling in hypothalamic cells [4]
  • 0.5-1.0 mM palmitate induces ER stress in adipocytes [5]
  • 0.3 mM palmitate leads to ceramide accumulation, inflammation and impairs insulin signalling in myotubes [6

But oleate protects against this:

  • 0.3 mM palmitate (but not oleate) causes mitochondrial dysfunction, insulin resistance, inflammation and substantially impairs viability of neuronal cells.  Pre-treatment with oleate completely protected against this and was more successful than linoleate (C18:2 n-6) or DHA [7]
  • 0.5 mM palmitate increases ceramide accumulation and apoptosis in CHO cells.  0.2 mM of oleate* was sufficient to protect against this because it promoted triglyceride storage rather than ceramide accumulation [8

* Information like this is really important.  How many meals have you had where the palmitate:oleate ratio is greater than 2.5?  Probably never!  Coconut oil and palm oil have a ratio of 1.38 and 1.19 respectively, and animal foods have a ratio of about 0.5 or lower

The article in Science Daily says “The reported findings predict the best time to eat a high-fat meal is early in the morning and probably the worst time is late at night” [2].  Cell culture studies are good for teasing out mechanisms, but I don’t think you should generalise the results from the petri dish to your dinner plate (and particularly in cell culture studies you shouldn’t generalise palmitate to all fat).  If inflammation, particularly postprandial inflammation is the issue, then I think the emphasis should be on consuming beneficial substances from whole foods (particularly fruit and vegetables) and reducing sedentariness (blog)

As for whether carbs of fat are better/worse at certain times of the day, that’s a question you’ll find many arguments or viewpoints for, and a topic for another day.  It’s also the kind of thing that people can experiment on for themselves quite easily and find what works for them

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