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.