Saturday, 19 July 2014

*How* does insulin cause weight gain?

The question of exactly how insulin causes weight gain is not intuitively obvious enough and so it needed testing, and thats exactly what this paper did....

Adipose Weight Gain during Chronic Insulin Treatment of Mice Results from Changes in Lipid Storage without Affecting De Novo Synthesis of Palmitate

They infused mice throughout the day with mini-pumps containing extra insulin. This lasted for 7 days until the mice were sacrificed and their fat stores examined. All mice were put on a low fat chow diet.

First to note, is that there was a non-significant increase in food intake in the insulin treated mice, although there was a slight trend to the upside.

LI= low insulin group,  HI= high insulin group

Surprisingly they did not detect any increase in the de novo synthesis rate of palmitate in the insulin treated groups. So the lipogenesis pathway was essentially unaffected by the insulin treatment. This could have been because the palmitate de novo pathway was already running at maximum capacity, amoung other possible reasons they present in the discussion.

Second, the insulin treatment mice had a persistent decrease in their blood sugar levels, this may have been what caused them to eat *non-significantly* slightly more.

Did the insulin treated mice increase their fat stores? yes....

Only the increase in the high insulin group's fat stores was deemed statistically significant. The punchline however is that the newly formed fat in the high insulin group came almost exclusively from newly synthesized triglyceride ( subQ depot ).  There was a slight decrease in lipolysis as well which also contributed to the net fat gain.

 Our findings indicate that insulin treatment likely reduced whole body fat oxidation rather than increasing de novo fatty acid synthesis, and altered TG deposition and lipolytic rates in different depots, but the whole-body macronutrient energetics responsible for insulin-induced increased gain in weight and adipose fat remain to be fully explained.

So... there you have it. Atleast in this model. Insulin causes fat gain by diverting fatty acids that would otherwise have been oxidized for energy to instead be assembled as triglyceride and deposited into your adipose tissue.

The applicability of this to real life weight gain in humans is (probably ) not a straight forward translation,, but I think you can rest assured that, in situations of large amounts of insulin floating around, your likely to find excess triglyceride accumulating in your subcutaneous fat.

Is our food more insulinogenic now than it was 50 years ago? And is everyone carrying more triglyceride than we were 50 years ago?.....................


  1. "This could have been because t"

  2. I am not 100% sure about food, but I think our eating pattern is more insulinigenic now than 50 years ago.

  3. Our food is "more insulinogenic" than 50y ago in part because we eat more of it, i.e. more calories.

    PMID: 19828708
    Am J Clin Nutr. 2009 Oct 14
    Increased food energy supply is more than sufficient to explain the US epidemic of obesity.
    "CONCLUSIONS: Increased energy intake appears to be more than sufficient to explain weight gain in the US population. A reversal of the increase in energy intake of approximately 2000 kJ/d (500 kcal/d) for adults and of 1500 kJ/d (350 kcal/d) for children would be needed for a reversal to the mean body weights of the 1970s. Alternatively, large compensatory increases in physical activity (eg, 110-150 min/d walking), or a combination of both, would achieve the same outcome.
    A Conversation With Carson Chow
    A Mathematical Challenge to Obesity
    Published: May 14, 2012
    "The [obesity] epidemic was caused by the overproduction of food in the United States. Beginning in the 1970s, there was a change in national agricultural policy. Instead of the government paying farmers not to engage in full production, as was the practice, they were encouraged to grow as much food as they could. At the same time, technological changes and the 'green revolution' made our farms much more productive. The price of food plummeted, while the number of calories available to the average American grew by about 1,000 a day. Well, what do people do when there is extra food around? They eat it! This, of course, is a tremendously controversial idea. However, the model shows that increase in food more than explains the increase in weight."

    1. Afterthought: I did not mean to say that I agree with those authors about higher calories being *the cause* of obesity. I was just backing up my assertion about higher calorie intake. Most of those calories are a blend of junk carb and junk fat.

    2. as I have pointed out on guyenet's blog and previously here, the association between increased caloric intake and weight gain does not have an obvious direction of causality.

      Keep in mind that heavier people have increased energy expenditures, and so calorie intake may have gone up BECAUSE energy expenditure has gone up ( and energy expenditure has gone up because people are heavier )

    3. "the association between increased caloric intake and weight gain does not have an obvious direction of causality."

      I agree -- re caloric intake *per se* (see my afterthought). However, the point in question had to do with the insulinogenicity of food, and I just said that our food IS more insulinogenic simply because we're eating more of it. That would always be true except if the increased food were entirely non-insulinogenic, like pure fat. Otherwise: more food = more insulin.

      Maybe the same (mass obesity, met syndrome, etc.) outcomes would obtain if people were eating large quantities of calorie-free insulin-releasing agents, such as some non-sugar sweeteners; i.e. maybe it has nothing whatsoever to do with calories. Though, as I turn this over in my mind, I think that that is unlikely. The extra calories (at least some extra calories) have to be there; you cannot gain weight on water, and adipose stores DO represent stored energy (calories). The calories are permissive, and necessary, but not causal. And also, as you point out, the calories are (past a point) the RESULT of obesity, as well. The idea that calories are the cause is a popular illusion and a seductive meme -- all the more seductive and tricky since there are modest elements of truth within it, and some observations (e.g. cal-restricted diet causes weight loss) are consistent with it. The truth is complex and very difficult (impossible) to express in sound-bite chunks -- which is why confusion and falsehood still reign, I'm sure.