Haha indeed.
Histamine plays an important part in heat production, energy balance/expenditure beyond leptin. So decreasing histamine signaling, as far as I know, decreases energy expenditure. But it's also important for leptin signaling pathway. And beyond that it also ties in many other processes revolving around energy balance/expenditure (brown adipose tissue, neuropeptides, etc.). I mean, blocking histamine as profoundly as mirtazapine does (it's the strongest antihistaminergic psychotropic drug to my knowledge) just wrecks pure havoc; from the immune system, energy expenditure to friking gut motility. It's why I said it's a dirty drug. I tried justifying it's use once to myself, so I did a little research, but this is as far as I went.
What's interesting though is that it kinda seems that people who have poor sleep (certainly something which is highly influenced through the histamine - orexin systems) seem to be more on the skinny side and have an easier time loosing weight and a harder time gaining weight. Might be a connection there involving, broadly speaking, histamine. And such people might not be at such a peril when using antihistaminergic drugs.
I'm to tired and today I've been on-line way beyond what's mentally healthy for me, so I can't further debate/research this (albeit interesting) topic now. But it certainly does disrupt leptin beyond increases in BMI and it certainly does predispose one to weight gain beyond pure increases in appetite (which is also down to mirt's 5HT2c antagonism btw, not just it's anti histamine action).
Leptin resistance has recently been confirmed not only in animal obese models but in human obesity. Evidence is rapidly emerging that suggests that activat
diabetesjournals.org