Is targeting thermogenesis a viable treatment option for obesity/metabolic disease?

Overweight people will have even lower surface area to volume ratio than normal people! 

At the moment several groups are trying to develop strategies to increase the "browning" of fat. There exist several reviews:

Mol Cell Endocrinol. 2013 Oct 15;379(1-2):43-50.

Nat Rev Endocrinol. 2014 Jan;10(1):24-36.

This review provides a nice explanation:

In the 1930ies dinitrophenol, a protonophore which "leaks" the mitochondrial membrane, was used in the US as a diet-pill. There were several fatalities because of lethal hyperthermia, and chronic use led to blindness due to cataracts. I think adverse effects of even a slight hyperthermia, if it 's chronic, could be prohibitive in humans.

Hi David. Yes, definitely. You will not be able to measure an increase in body temperature - at least not systemically. Thus, re-activation of brown fat in humans - or maybe generating some active "beige" fat - represents one on the most promising and exciting approaches to fight obesity. Best wishes from Vienna, -harald

One can also take L-Thyroxine to push the levels closer to the upper end of normal spectrum, which is more than likely to use up reserve energy (provided the intake remains the same), just as wasting energy by fooling the normal thermogenesis. Both approaches have similar theoretical potential and both are dangerous in the long-run.

Rather than "promising", a sure way to control obesity has always been the "boring" consumption of balanced diet combined with exercise.  ;)

Hi David!!. I think that at this moment this is hot topic in obesity field. Since several years ago that it was demonstrated that humans, under certain circumstances, could reactivate, the capacity to dissipate heat is fantastic by BAT. I remember you that scientific community thought for a long time that BAT dissapeared after birth in humans. Then, since 2009, BAT reactivation is one of the most exciting possibilities for burning fatty acids in mitochondria by increasing non-shivering thermogenesis

The nice article i have read recently

Moisan A, Lee Y-K, Zhang JD, Hudak CS, Meyer CA, Prummer M, et al. White-to-brown metabolic conversion of human adipocytes by JAK inhibition. Nature cell biology. 2014

Is a very interesting topic today. As per Herald, yes,  we may not be able to measure the temperature rise but using K4B2, we may measure the energy expenditure , change in  RQ  and the diet Induced thermogenic effect of specific food or ingredient. BAT is related to mainly adoptive thermogenesis for cold.

Use of L-Thyroxine may be an easy way of loosing body wt for normal people but if the obesity is resistant type due to hypothyroidism, L-Thyroxine will not be effective .

Levothyroxine will lead to weight loss in Hypothyroidism primarily by facilitating weight loss by other means. Furthermore there are TH receptors in brown fat that suggests physiological role for thyroid hormone. In hypothyroid state weight loss induced by TH is not always related to thermognesis alone. Loss of retained fluid and better water clearance through improved renal blood flow are other reasons.

although most of research on obesity is concenrating on white adipose tissue and the development,differentiation ie hypertrophy and hyperplasia of adipocytes and pfeadipocyytes in WAT and role of inflammation and macrophage infiltration directly or conversion of preadi[ocytes,metabolic endotoxemia,gut microbiota lreading to increased LPS absorption from increased GIT permeability with altered gut microbiota is some of the aetiopathogenesis with infiltration of Treg cells,cdt4. CHT8 cellsiNKT CELLS th17 all have ben found but importance is being given simultaneously to the microrna which affect the differentiATION OF BRITE AND BROWN ADIPOCYTES AND IMPORTANCE OF MIrna'S 26,155,27a,b,130 a ,miR155 etc in adipocyte differentiation and how further roles of FGF21 may affect thermogenesis and natriureteic peptides

I agree that browning of white fat is one of the most promising options in reducing obesity through mechanisms of uncoupled respiration but it is well established that the mechanisms of thermogenesis in humans is different from that in rodents. There is evidence that in humans a significant amount of heat is produced by skeletal muscle and the actions of Uncoupling Protein 3 (UCP3).  One interesting idea is to look at the actions of UCP3 in skin, where it is endogenously expressed.  Our lab has data suggesting that overexpression of UCP3 in skin is sufficient to lower body weight and prevent diet-induced obesity.  There does not seem to be a change in body temperature in these animals presumably because they are able to dissipate excess heat externally.