Tuesday, April 19, 2011

Set to Be Obese!? Dopamine Turns Out to Be Another Major Player in the Neurological Orchestra of Obesity

As I promised, I am trying my best to keep up with current research on the neurological aspects of obesity, I also talked about on Carl Lenore's Super Human Radio on March 31, 2011. While the focus of the previously mentioned study was on the less well-known relationship between inhibitory and excitatory neurons in the hypothalamus, the major player scientists from the University Medical Center at Leiden in the Netherlands studied is a rather famous one: Dopamine.
Figure 1: Basal glucose & insulin levels in DIO & DR mice after 2 weeks on placebo (P), bromocriptine (B) or haloperidol (H) (data adapted from de Leeuw van Weenen. 2011)

What de Leeuw van Weenen et al (de Leeuw van Weenen. 2011) found in the same diet induced obesity [DIO] mouse model Ravussin (Ravussin. 2011)had used in his study (cf. Follow Up on Set-Point Theories: Could Royal Jelly Help With Obesity / Diet Induced Structural Brain Changes?) were
  • altered dopaminergic transmission
  • exaggerated basal and feeding-evoked dopamine release
  • reduced dopaminergic receptor (DRD2) activity and number of binding sites
This obesity-related modulation of DRD2 activity has been shown to have ...
[...] profound effects on energy homeostasis in humans and animals. Drugs that blockDRD2 enhance appetite and induce weight gain in animals and human. Conversely, DRD2 agonist drugs reduce body weight, increase energy expenditure, and improve glycemic control in obese animals and individuals.

To verify the efficacy of respective drugs, the researchers administered Bromocriptine (DRD2 agonist) and Haloperidol (DRD2 antagonist) to DIO and diet resistant [DR], i.e. naturally lean mice, and found that ...
It does not take Bromocriptine
for dopamine-agonism.
L-Dopa from Mucuna Pruriens
is a natural and proven
precursor to dopamine.
Haloperidol treatment reduced the voluntary activity and energy expenditure of DR mice and induced insulin resistance in these mice. Conversely, bromocriptine treatment tended to reduce bodyweight and voluntary activity, and reinforce insulin action in DIO mice.
Taken together these results / effects of reduced dopaminergic tone
  • decreased insulin sensitivity, hyperglycemia
  • decreased voluntary movement and slowed metabolism
  • decrease in dopamine induced "reward" (satiety) after eating
further establish the unfortunate truth that the neurological abnormalities that go hand in hand with diet induced obesity eventually set you up to stay overweight or, worse, to become even more obese.