Obesity and diabetes (2) Basal lipolysis and weight gain

This is a paper at the "dislike" end of my bias spectrum:

In Vitro Lipolysis is Associated with Whole Body Lipid Oxidation and Weight Gain in Humans

which can be summed up by the first line of the introduction

"Positive energy balance results in greater triglyceride storage in adipose tissue and resultant accumulation of body fat."

which explicitly states that they have the arrow of causation at 180 degrees to the correct direction. So don't expect too much from the paper. I also hate that they omitted to mention in the title that the association with weight gain is negative.

Beyond that the methods are sketchy and the results are limited to a number of model derived correlations subjected, eventually, to multiple unspecified adjustments. So not a lot of hope for the group or for the largely Pima Indian population under their misguided care. But I digress.

Once again adipocyte size is quite tightly correlated with basal lipolysis, like this

which looks quite linear until we convert the log numbers to normal numbers like this

which shows us that basal lipolysis rises progressively sharply with adipocyte size. There is an upper limit to adipocyte size, and this will be set by rising basal lipolysis equaling the obesogenic effect of linoleic acid facilitating the over action of insulin.

They fed the subjects a fixed macro, calorically calculated diet for three days before a day in a metabolic chamber, where they ate three similarly fixed macro/calorie meals.

People turned out to have differing RQs (they use RQ, respiratory quotient, as their term rather than RER, respiratory exchange ratio. My brain works this way too, it's about the only bit of the paper I like, even though RER is probably the correct term) on a fixed macro diet. So clearly something is happening on a fuel partitioning basis.

People who oxidised the most fat in the metabolic chamber were the least likely to gain weight over the following eight or so years. Those oxidising the most carbohydrate were likely to gain the most weight.

Funny that.

I can't see any explanation in the discussion of why that might be.

From the ROS/Protons perspective it is quite clear that people with smaller adipocytes have not finished gaining weight. They are part way to becoming obese because they are consuming LA in combination with an insulogenic diet so are over-storing fat. When they eat a fixed macro/calorie diet they sequester lipid in to adipocytes, fail to retrieve it and run their metabolism on the more accessible carbohydrate. They're probably the most hungry, in my book.

Those with maximum sized adipocytes eat the same fixed macro diet, sequester the same lipids in to their large adipocytes via LA augmentation of insulin's fat storage signal but then go on to release much of that extra stored fat by the increase in basal lipolysis which is associated with trying to further stretch large adipocytes. This supplies continuously elevated FFAs, with subsequent fat oxidation, despite the presence of glucose and insulin at the same time. They should be the least hungry.

What can a cell do when presented with a ton of FFAs and a ton of glucose, both having their uptake facilitated by insulin?

That's right. Resisting insulin is the correct option. That's what the systemic cells do.

The cost shows as elevated glucose in combination with the elevated fat oxidation (eventually FFAs rise measurably but early on the fat oxidation increase precedes the rise in plasma FFAs).

It is metabolic inflexibility encapsulated.

Of course the obvious question is whether that increased fat oxidation, associated with reduced rate of weight gain, is positively associated with insulin resistance. Alongside the reduced weight gain.

From the same institution, back in 1991 and forgotten about during the last 30 years, we have this paper:

Insulin Resistance Associated with Lower Rates of Weight Gain in Pima Indians

Insulin resistance is, indeed, associated with limited weight gain. As you would expect.

Summary overall:

Fat oxidation a major mechanism of insulin resistance. Increased basal lipolysis is a mechanism of both increased fat oxidation and decreased weight gain. Linoleic acid is the mechanism of increased adipocyte size to drive increased basal lipolysis. Some degree of insulin signalling is essential for linoleic acid to drive adipocyte size increase.

Life is logical.

Peter

Extra thoughts: During weight gain, while calories are being lost in to adipocytes, the rest of the body is in caloric deficit. Calories lost to adipocytes must be replaced by extra food. This is the correct arrow of causation. There is insulin sensitivity.

Once adipocyte basal lipolysis equals or occasionally outstrips fat sequestration in to adipocytes, the rest of the body is being provided with supplementary FFAs. It is in caloric surplus. Insulin resistance is then physiologically appropriate.

There is a gradual transition between the two states.