For a long time, the melanocortin system was basically thought to control the color of skin and hair. It still does, and many redheads are redheaded due to polymorphisms in one of the melanocortin receptors.
Fast forward to 2015: to make a long story short, melanocortins are HUGE players in circadian biology.
Brief background (also see figure above):
Fed state -> high leptin -> a-MSH -> MC4R (the receptor for a-MSH) = satiety, energy production, fertility, etc.
Fasted state -> low leptin -> AgRP blocks MC4R = hunger, energy conservation, etc.
MC4R polymorphisms in humans are associated with obesity. Melanotan II causes skin darkening (marketed as “photoprotection” [no bueno, imo]), enhanced libido, and appetite suppression.
Posted in Advanced nutrition, angiotensin, Bromocriptine, Cabergoline, chronopharmacology, circadian, fertility, insulin, melatonin, sleep, Sun
Tagged carbs, circadian rhythm, diabetes, diet, insulin, melatonin
Part I: Circadian Mismatch
1. Artificial light at night suppresses melatonin (Lewy et al., 1980); induces “circadian mismatch.”
2. Circadian mismatch is associated with and/or predisposes to breast cancer (eg, He et al., 2014 and Yang et al., 2014).
3. In this epic study, human breast cancer xenografts were exposed to blood taken from healthy, pre-menopausal women during the day (melatonin-depleted), at night (high melatonin), or at night after light exposure (melatonin-depleted) (Blask et al., 2005). They showed that tumors exposed to melatonin-depleted blood exhibited higher proliferative activity than those exposed to melatonin-repleted blood. This has been deemed one of the most “ethical” studies to demonstrate a causal link between circadian mismatch and cancer.
4. And to make matters worse, circadian mismatch also reduces the efficacy of cancer drug therapy (Dauchy et al., 2014). This study showed that, in a rodent model of breast cancer, exposure to light at night (circadian mismatch) enhanced tumor development and induced tamoxifen-resistance, and this was abolished by melatonin replacement.
They also suggested a mechanism: tumors metabolize linoleate into the mitogen 13-HODE. Melatonin suppresses linoleate uptake.
“When we block the D2 receptor in humans, it is expected they will develop glucose intolerance, obesity, and sedentary behavior.” -Jane Plain, in her series on The physiology of body fat regulation. It’s probably true.
Randomized pilot study of cabergoline, a dopamine receptor agonist: effects on body weight and glucose tolerance in obese adults (Gibson et al., 2012)
Cabergoline is primarily used to treat prolinactinoma, or prolactin-secreting tumors. In women (& men apparently), prolactin stimulates milk production; in men, it is associated with the refractory period after orgasm. In both genders, dopamine inhibits prolactin secretion. Cabergoline targets the D2 receptor, but it’s a dirty drug. It’s used off-label for gyno and to improve sexy times (Kruger et al., 2003 <– yes, that was actually tested).