Vain 68, let me see if I can clear up a few things for you. Alpha and beta-adrenergic receptors do not become insulin resistant, insulin receptors become insulin resistant. Alpha and beta-adrenergic receptors are agonized (stimulated) by catecholamines such as epinephrine, norepinephrine, and ephedrine. Stimulation of alpha2-adrenergic receptors in the pancreas will inhibit insulin release which is good if we are trying to burn fat. However, overstimulation of alpha-2 receptors will inhibit further norepinephrine release which will result in less fat oxidation which we don’t want. Dan Duchaine once taught that fat in the the hips, thighs, and “love handles” had a higher alpha-2 adrenoreceptor profile which is why it is harder to lose fat in those areas even though I have not seen any data to prove this. This is why he originally suggested that yohimbine(alpha-2 antagonist) should be used for people trying to rid themselves of those hard to lose areas. The love handles, lower abs in both sexes, and hips and thighs in women are usually the last to go. Obviously there is something metabolically and pharmacologically different about them which is why they are the last to go on a strict diet. Naturals who lower their calories even more to lose them often sacrafice a lot of muscle tissue to do so. Now beta-adrenergic stimulation has been shown to inhibit glucose uptake in a post-receptor mechanism which has not been fully elucidated yet. Taking ECA may inhibit fat loss by stimulating beta-receptors and increasing blood sugar levels. However, we know that ECA will also greatly increase lipolysis which is thought of as the limiting factor in fat loss. So it is kind of like one step back, two steps forward. I believe that the fat loss effects of ECA (forget about taking the “A” though) outweigh any negative effects it may have on blood sugar, but only in active people. Yohimbine is similar. Blockade of the alpha-2 receptor will result in higher insulin release from the pancreas but will also result in increased norepinephrine release which will increase fat oxidation and in theory help you lose those “love handles”. Insulin resistance is correlated with primarily a increase in visceral but not subcutaneous fat as is high cortisol levels even though there is some evidence that high cortisol may inhibit some subcutaneous fat loss as I mentioned in a pevious post. Leptin resistance is most often correlated with high subcutaneous levels. If you could find a way to increase leptin release or sensitivity that would probably be the most effective ways to lose those tough spots. Lyle McDonald believes that bromocriptine will take the place of leptin but I am not convinced after looking up some of his references. I believe dopamine and dopaminergic agonists will prove effective for fat loss but I don’t believe they are primarily responsible for leptins effects. Right now we know that the best way to improve leptin release and sensitivity is to maintain good insulin sensitivity, low blood sugar, and low-insulin levels as all will improve leptins effects. As long as a person is actively exercising I do not see a major problem with taking ephedrine, caffeine, or yohimbine as long as they are at the recommended doses and you don’t mind the side effects (which I don’t enjoy). For an inactive person their negative effects on blood sugar and pressure would outweigh their positive effects on weight loss. If we could develop an orally active, highly selective beta-3 agonist, most of these problems would be solved because they increase glucose uptake and increases lipolysis without the side effects of other adrenergic agents. They can decrease the release of leptin though. There always seems to be some give and take when it comes to fat loss. The bottom line is we are still a long way from understanding the fat loss puzzle but as we recieve more pieces the puzzle is becoming clearer. For someone trying to lose those tough spots I would recommend trying yohimbine starting at a low dose of about 5 mg daily and working up to 15-18 mg. Alternatively one could try bromocriptine, like Lyle Mcdonald recommends, or another D2-agonist like vitex. I would be interested to see how that works for people, especially the vitex. I would also avoid carbs, but I would eat just enough to stay out of ketosis. Carbs should come mostly from fibrous low-glycemic sources in the morning. Also take in high omega-3 fatty acids (DHA and EPA), high calcium(1000-1500mg), and lots of milk proteins (whey and casein). Vain68, I do not believe at this point that poor insulin sensitivity is the reason people have a hard time losing those problem spots except perhaps in people on a higher carbohydrate diet. It is probably from some other genetic difference such as increased alpha-2 expression or decreased leptin sensitivity in these tissues. Unfortunately, there is not many research dollars going into figuring out how to lose love handles as these don’t present as big a health risk as visceral fat. Sorry it took such a long explanation to get to this point.