From this paper we learn that SOCS3 inhibits the actions of leptin in the brain by binding to the leptin receptor there. Not good!
Next, we see from this paper that obese people have elevated levels of SOCS3, as shown in the graph below. ( grey bars = obese subjects, black bars = lean subjects )
The whole thing is further complicated by the fact that the liver secretes a protein sOb-R that binds to leptin and makes it inactive. This whole stuff was talked about by Peter back in this post. Blah it seems I am late to the party once again! I am making this post rather just to drill this stuff into my head. It seems the reason that the LIRKO mouse is not fat is because it pisses alot of glucose ( calories ) out via glycosuria and the mouse is also super sensitive to leptin via very low SOCS3.
Interesting.
ReplyDeletePersonally I am not against a functional sort of leptin signalling inhibition being part of obesity, and certainly would be consistent with my history. My belief that leptin resistance is false, is the hypothesis that the leptin receptor is defective in obesity as Jack Kruse is apt to promote. My leptin receptors appear to be otherwise unremarkable, my leptin sensitivity appears to fluctuate with energy use (e.g. ketosis or not)... and certainly obesity does not manifest as a syndrome of total leptin resistance as true leptin insufficiency features specific phenotype that is inconsistent with regular obesity. Praeder willi patients are more like a leptin deficient/reistent model than a regular obese person, due to the fact they have persistent abnormalities indicating starvation like delayed growth and hypothyroidism and not entering puberty normally and a bias to build fat not lean tissue specifically, and very high ghrelin ...all suggesting leptin signalling is not happening at the brain level at all.
Weight reduction is known to increase leptin inhibiting proteins, which further causes post weight loss metabolic / appetite abnormalities (in addition to absolute relative hypoleptinemia).
Aye I have posted about many things on this blog which would appear to be "the" cause of common obesity. However only one of them can be right!
ReplyDeleteWell, if obesity is a symptom of a messed up system, maybe there is more than one cause. Once 60 patients were.examined with an endoscope and proven to have stomach ulcers. They were one by one then examined by a chinese healer who knew nothing of the scope findings. He found by a purely eastern observation with no modern equipment many different "system imbalances, malnourishments, and toxic levels". After rxing several different herbal remedies, he boasted an 89% cure rate. The endoscope confirmed this. So many various issues resulted in one common symptom, but without one common cure. (Dean Black out of Berkley) I often wonder if one reason so many argue in circles over obesity cures might be that its a.mere symptom specific to many different endocrine problems? I wonder.
ReplyDelete