Drug-Activated Thyroid Hormone Receptor Promotes White to Brown Fat Conversion - [Research Report]
Recall from a recent post that I told you that unlike white fat (the one on your belly), brown fat dissipates energy as heat instead on harnessing it through the ATP synthase in the electron transport chain within the mitochondria. One of the key players in this energy dissipation is UCP1 or Uncoupling Protein 1.
In a relatively widely cited study from 2015, Phillips and colleagues sought to demonstrate how the activation of thyroid hormone receptor by a synthetic agonist (GC-1) induces adaptive thermogenesis in white fat in vivo and the browning of white fat in vitro (at least).
What they did:
- they fed ob/ob mice (genetically engineered to be obese) a diet containing GC-1 or a control diet
- they also used C57Bl/6 mice and UCP1-/- (knock-out) mice to investigate UCP1 expression
- they looked at changes in gene expression of adaptive thermogenesis genesis gene and mitochondrial function in brown fat, epididymal white fat and subcutaneous white fat
What they found:
- GC-1 elicits a BAT-like program of adaptive thermogenesis in subcutaneous white fat of ob/ob Mice
- unaltered UCP1 protein levels in BAT with GC-1 treatment
- 100-fold increase of UCP1 in subcutaneous fat with GC-1 treatment, equivalent to ~40% of that in BAT; a 'striking' finding indeed
- undetectable UCP1 in epididymal white fat in both treated and untreated mice
- GC-1 thermogenesis depends on UCP1 (for this they used the knockout mice)
- they also observed that browning of white-fat by GC-1 is cell autonomous
- browning of subcutaneous fat induced by GC-1 coincides with marked thermogenesis and metabolic elevation. Funny, they looked at body temperature after GC-1 treatment:
"GC-1 raised metabolic rate by nearly 60% (Figures 2A and 2B) and increased body temperature by 3.8C (Figure 2C), an increase that was readily apparent when handling animals." [source]
- less funny, but very important findings:
"The induction of thermogenesis was accompanied by marked weight and fat loss. GC-1 treatment did not alter food intake, and treated mice were marginally less active than untreated controls, indicating weight loss resulted solely from increased metabolic rate. Lean mass increased following GC-1 treatment, indicating weight loss was due exclusively to a loss of adiposity. GC-1 treatment also led to a substantial decrease in the respiratory exchange ratio (RER), with values approaching the theoretical minimum of 0.7, indicating that GC-1 elicited a substantial shift in substrate utilization from carbohydrates to fatty acids." [source]
- analyzing the accompanying graphs and figures by reading the full paper will give you clue of these interesting findings.
Modulating the activity of the thyroid hormone receptor seems to play a central role in mammalian metabolism; I think we have sufficient data from the past century of research to support the fact that similar effects may occur in man; currently, this type of study is harder, to say the least, to replicate in humans, but I think it gives enough clues for exploring further research venues.
As Phillips et al. (2015) report, GC-1 mediated TR activation induces a BAT-like adaptive thermogenesis in non-BAT (scWAT) fat:
"This action, which is accompanied by a marked increase in metabolism, fat loss, and increased cold tolerance, suggests browning of WAT may represent an unappreciated component of TR-induced thermogenesis." [source]
They also seem to agree on the translation-ability of these findings in humans:
"Given that GC-1 can increase adipocyte metabolism in a cell-autonomous fashion and has been shown previously to evoke weight loss in non-human primates (Grover et al., 2004), we believe there is strong potential that these results could be translated to man." [source]
Until further research, I suggest reading the full open paper (with the methods, materials, discussion, graphs, etc), because I could only summarize 'so-much' in this short post. You can find it here:
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Cristi Vlad, Self-Experimenter and Author
A really good subject. Thanks for sharing it. Upvoted, resteemed and followed.
Amazing what we have 'learned' over the past century about animal physiology and the potential to alter the course of disease, genetic evolution and eugenics.
It would seem to me, that we are scratching the surface of a hierarchy of knowledge way beyond our capability to perceive.
In light of Man's history of scientific and medical blunders, any list I could produce would simply serve to project an understatement, it seems we play with more than just fire and we modify the future of Man's physiology.
We seem to have little regard for those who are experimented on either. The US government has a prime example in the irradiation of troops and civilians during its first land-based nuclear tests, not to mention the incredible impact on the planet and it's ecology in all nuclear testing.
But that of course, is the least example, dramatic by comparison and well known, but most experimentation and interference involves food additives, genetic modification, preservatives, pesticides, colorants, flavorants, climate changing activities, deforestation, destruction of millions of species daily, disruption of every ecosystem in existence and indoctrination with malicious intent.
While these developments are exciting and most welcome, my mind always warns me that Man is no match for the creativity displayed in the existence of life as we know it and our intervention in the course of 'evolution' has dire consequences in almost every instance.
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