Sunday, May 19, 2013

Overweight but Insulin Sensitive and Normal Weight but Insulin Resistant: Part 2

Adipocytes and Weight Gain 

Adipocytes have three general responses to an increasing level of triglyceride storage 

  • Hypertrophy (getting larger)
  • Hyperplasia (dividing, therefore more cells)
  • Letting someone else deal with the problem (muscles, liver, etc) 

Hypertrophy, filling up and overflowing, caused the insulin resistance (beginning with the adipocytes) and other problems I mentioned in part 1.  Letting someone else deal with the problem just increases insulin resistance in the other tissue(s).  Hyperplasia doesn’t increase insulin resistance, it just forestalls it (assuming you’re going to keep gaining weight). 

It’s well known that weight gain generally increases insulin resistance and inflammation.  While someone is gaining weight there’s some hypertrophy and some hyperplasia.  The hypertrophy (not the hyperplasia) increases insulin resistance and inflammation.  Remember that large adipocyte cell size is a characteristic of insulin resistant obesity [1] [2] 

* One of the features of insulin resistant obesity is something called adipose tissue dysfunction, which is generally described as a hypersecretion of signalling molecules that promote insulin resistance, inflammation and atherosclerosis and less secretion of protective signalling molecules (such as adiponectin).  One component of adipose tissue dysfunction is an inability to generate new adipocytes (adipogenesis), which in turn leads to larger adipocytes (assuming weight gain) and the host of problems mentioned in part 1 [2]. 

Adipocytes and Weight Loss 

It’s also well known that weight loss generally reduces insulin resistance and inflammation, and often quite a large effect.  This seems to mainly be due to weight loss reducing adipocyte cell size but not adipocyte cell number as much [1]. 

This can present an interesting situation: people who were previously obese then have lost that weight and now have a normal weight have a smaller adipocyte cell size than weight matched controls, which promotes insulin sensitivity.  European Americans who were previously overweight were more insulin sensitive than weight matched controls.  However, this relationship was the opposite for African Americans [3], which suggests a strong genetic influence in all of this. 

Adipocytes and Leptin Signalling 

If you’re a European American I wouldn’t suggest that you try to improve your insulin sensitivity by gaining weight first and then losing it.  The reason is that leptin release is largely determined by adipocyte cell size [4], so in the case formerly obese very insulin sensitive there isn’t as much leptin released compared with weight matched controls. 

To use an extreme to help make the point see the table below:


While leptin is a pro-inflammatory cytokine, it does also help you maintain a stable body weight.  This can help explain how: 

  • Simple calorie restriction without changing anything else is so difficult to sustain, as eating less and reducing adipocyte cell size will substantially lower leptin release
  • People who were previously overweight have a harder timing maintaining their weight
  • Weight loss from obesity is more difficult as you approach your target weight (which may be especially true for people with insulin sensitive obesity* and may also explain a very anecdotal observation I’ve made that women -who more often have insulin sensitive obesity - tend to have a harder time than men in getting to an maintaining their target weight*)

Assuming the above is correct this would mean:

 

* Speculations


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