In previous blogs I have spoken to the importance of bench science -- the kind done in the lab to decode the “basic” science that underlies human physiology -- to us as clinicians and to us as patients. And the branch of the sciences which explores the connection between bench science or lab science and clinical medicine, including mental health, is called translational medicine.
This last night I couldn’t sleep. This happens to me when I have any viral illness and I have learned to just give up and carry on reading, rather than tossing or turning. While initially tossing and turning, however, my brain began reviewing the tiny drop in the ocean of current information about insulin resistance, leptin, obesity and anorexia nervosa to which I am privy. I began to worry about a couple of our (recovering) patients with metabolic problems.
So, as I threw off the covers and reached for my computer, I asked myself: should I open Netflix and watch Midsomer Murders (again) for a glimpse of glorious English gardens (something that means a lot to me), or should I review Wikipedia’s article on insulin resistance and GLP-1 agonists? OK, Wikipedia it is.
I started reading. Through the magic carpet that is the Web, one article lead to another: from the sublime (PubMed) to the humble (individual doctors’ blogs), I began tracing leptin resistance and weight balancing. I stumbled across a blog by someone named Dr. Sharma. One entry was called “unfolding leptin resistance”. I read it and clicked on the live link to an article in Cell Metabolism. I wound up inside Pubmed reading an abstract called “Endoplasmic reticulum stress plays a central role in development of leptin resistance.”
Huh? The darned endoplasmatic reticulum? Not what I expected. Now, I did study biology long ago and even then there was the endoplasmatic reticulum (ER), part of the cell’s mechanism for translating proteins from genetic instructions and manufacturing them in order to do, well, everything. I did not know that the ER could experience stress. What the heck was “ER stress”?
Back to Wikipedia for a dense but enlightening article about such stress, at the end of which was mention that there was a reciprocal link between obesity and ER stress. This revelation lead me back into the heart of Pubmed and an abstract called “Possible involvement of endoplasmic reticulum stress in obesity associated with leptin resistance”.
Now that is right up our alley, since in pursuit of what we at Kartini Clinic like to call “Weight Restoration 2.0”, we have noticed that some of our patients recovering from anorexia nervosa struggle to recover adequate leptin levels. And some of our other patients with binge eating and higher body weight seem to struggle with what we think is leptin resistance.
I then read about something called the “unfolded protein response” (UPR), apparently key to the stress on the endoplasmatic reticulum. UPR is a response to the situation whereby certain environmental pressures (such as the prions of two terrifying diseases: BSE aka “mad cow” and Jacob-Creutzfeldt) or certain genetically predisposed conditions (Alzheimer’s, Parkinson’s and other common neurodegenerative disorders) cause proteins of defective shape to be produced.
Remember, proteins are large complex molecules which the cell folds in exact ways in order for them to move through cell membranes and carry out their critical functions. When they are wrongly folded, all hell breaks loose. The cell does not tolerate this and has several mechanisms to denature (deconstruct) such defective proteins, but at some point, if there are enough poorly folded proteins, the cell itself is targeted for death (apoptosis). Enough brain cells die and you get the devastating effects of the above-mentioned diseases.
Who among us knows no one with Alzheimer’s or Parkinson’s? What fate awaits many of us in the form of a brain disorder? And before you think that you personally are a long way from any of these, please recall that eating disorders are brain disorders of entirely unknown etiology (cause).
Further insomniac surfing and I stumbled across an article in the BBC “Alzheimer's breakthrough hailed as 'turning point“. The authors report on a study in mice where they were able to administer a drug which reversed completely the neuron-killing effects of misfolded proteins and ER stress. I clicked excitedly on the link to Science Translational Medicine: folks, if this pans out, it’s going to be very good news for us all.
So from leptin to thinking about obesity and it’s evil twin anorexia, to the endoplasmatic reticulum and its surprise relevance to the metabolism of weight restoration, to brain disorders being reversed by medications already in the pipeline basic science will save us all. In my opinion, no course of study relevant to humans -- whether medicine, psychology or dietetics -- should be illiterate in the language of biology. After all, biology “R” us!