Wednesday, 28 March 2012

Dopamine fat loss

Whats the connection between Dopamine and bodyfat? The answer seems to be the sympathetic nervous system.

The receptors that dopamine acts on in the brain sends a signal down the nervous system much like electricity down a copper wire to the targeted group of fat cells, whereby some triglyceride is subsequently kicked out of the central lipid droplet and is then chopped up by lipases in the cytoplasm, breaking it down to fatty acids + glycerol.

Much attention is often paid to the circulating factors in the blood that influence fat cell size, like insulin, acylation stimulating protein, epinephrine etc etc. But the connection of fat cells directly to the brain by the nervous system is often overlooked, And this connection is also reported to be a major source of lipolysis.

This paper talks about the Siberian Hamster that is seasonally obese, it is fat in the summer when the days are long and lean in the winter when the days are short. The brain is able to keep track of this seasonality by the duration of the nocturnal secretion of melatonin. However, melatonin itself does not stimulate lipolysis when cultured with fat cells.

Despite much investigation into the blood circulating hormones that where known to affect fat cell size, none of them were able to account for the dramatic change in bodyfat seen in the Hamster in response to season changes. The logical conclusion from this was that seasonal obesity was almost completely controlled by nervous system lipolysis.

It seems that in addition to dopamine, the nervous system wires coming from fat cells and ending in the brain also express melatonin receptors, and melatonin hitting these receptors triggers additional lipolysis. This is actually surprising to me, as when I was supplementing melatonin to help cope with shift work I could swear I was gaining bodyfat. I will admit though at the time that I was still eating a junk food diet, that was very insulinogenic.

Insulin really is the daddy you know.

I think this also explains why reduced sleep is linked to obesity, less melatonin reduces lipolysis, giving the chance for fat cells to increase in size the next day when you eat normally. Could it be the same principle for why dopamine blocking drugs cause weight gain? Its not that blocking dopamine causes fat storage, but rather, it greatly inihibits fat break down. The paper also mentions how blocking this nervous system activation causes less lipolsis when fasting.


  1. Melatonin promotes metabolic syndrome. It will suppress dopamine and lead to glucose intolerance.

    Melatonin is a seasonal indicator like dopamine, indicating shorter photoperiod (season change into fall) which leads to glucose intolerance to conserve energy for the stressful, less nutritionally replete winter season. Melatonin, metabolically, is the opposite of dopamine.

    The paradoxical thing about metabolism is that things hwich increase fat burning are the things that sometimes lead to obesity. Doapmine insufficiency, which goes along with melatonin dominance, also leads to heightened lipolysis, as if preparing for a famine where one will be using body fat for energy (and, while still eating food, storing it as fat due to an inability to use glucose because of melatonin dominance/dopamine insufficiency/sensitivity)

    Seasonally obese hamsters also respond to melatonin with weight gain, as well as infertility, as if preparing for starvation:

    Furthermore, bromocriptine (dopamine d2 agonist) prevents seasonal obesity in these hamsters:

    Human beings will also have suppression of fertility via melatonin, and we also respond with glucose intolerance and fat gain. SEasonal obesity is not binary, it is a gradient. Human beings still do respond to melatonin like animals, and we also respond to low dopamine (redunant with high melatonin).

    In general, melatonin promotes a starvation syndrome, hibernation /seasonal adaptation - like changes (glucose intolerance, infertility) whereas dopamine suppresses these changes. Light makes dopamine on blast, lack of light makes melatonin dominant. Furthermore dopamine suppresses melatonin, and melatonin suppresses dopamine. These are very much major neuroendocrine signals that regulate not only the circadian rhythm but body weight, food intake, glucose tolerance, fertility, and generally program our bodies to seasonally adaptive metabolic states.

    PS starvation at any time of the year results in lower dopamine levels and high central melatonin levels. These neuroendocrine mechanisms can be tripped by starvation, not just potential starvation (e.g. waning light).

  2. Woo thanks for that melatonin paper that confirms my suspicion, afternoon melatonin supplementation was helping me sleep at night but I also noticed my waist expanding 0o

    In contrast to the hamster I also noticed over the years its been much eaiser for me to lose body fat in the summer, where as losing bodyfat in the winter is wwwaayyyyyy harder.

  3. My body weight and glucose control and mood is infinitely superior in the late spring/summer.

    I have no ability to tolerate melatonin, although in my case the metabolic / weight / appetite effects are the smaller part... I find it terribly triggers my mood disorder.

    5-htp can increase melatonin and you may find it much more tolerable as it support serotonin signalling, and central endorphins and stress hormones thereby, which can help counter-act the obesigenic / central stress depressant nature of melatonin otherwise. I only seem to be able to safely tolerate 5-htp every other day. I have been experimenting for years and if I take it more than this I develop signs of winter depression and metabolism fail... but at this very low dose it helps make me feel a bit more peaceful and centered and sleep better.

    If you are a shift worker and have trouble sleeping I STRONGLY suggest getting black out curtains for your sleeping area, and a light box for your waking hours. I am also a shift worker and when I combine the light box with the curtains I do rather well, and can sleep just fine assuming I eat enough calories to inhibit my stress response.