obesity sans overeating :(

As stated in the Laws of Energy Balance, you can get fat without eating more, and unfortunately there are about a thousand different ways to do so.  Here is yet another:

Long-term, intermittent, insulin-induced hypoglycemia produces marked obesity without hyperphagia or insulin resistance: a model for weight gain with intensive insulin therapy (McNay et al., 2012)

While it has a lot in common with fat gain diet-induced insulinemia and diabetic insulin therapy, this isn’t the greatest “model for weight gain with intensive insulin therapy.”  But it’s an interesting one nonetheless.

chocolate peppermint doughnuts

In this model, normal rats are fed the standard fare, but once weekly get jabbed  with 10 U/kg insulin; enough to drop glucose to ~35 mg/dL (seriously hypoglycemic).  Yes, this is an insulin spike, but not like the ones we normally see – usually, carbs cause the insulin spike but also provide the glucose necessary to prevent hypoglycemia.  These rats weren’t so lucky.


In humans, hypoglycemia is prevented/managed by the counterregulatory response, although repeated bouts of hypo impair this response (known as hypo-associated autonomic failure HAAF).  Apparently something similar happens in rats… in the beginning, it took 10 U/kg ‘slin to make them go hypo.  By the end of the study, the rats either became drastically more insulin sensitive (unlikely given their robust increase in body fat), or they too experienced HAAF because it only took 0.5 U/kg to get them down to 35 mg/dL.

Anyway, the results were ridiculous:

BW FI

RH (repeatedly hypoglycemic) rats are massively fatter despite utterly identical food intake.  How is this possible?  Hint: it’s got nothing to do with glucose tolerance:NGT

THIS: insulin spikes totally bollixed energy expenditure.  HAAF rats can barely tolerate a cool breeze (impaired thermogenesis), and all their food intake goes into fat tissue, leaving none leftover to fuel any fun activities.EE

Diets that promote greater reductions in insulin preserve energy expenditure (eg, Metabolic rate per se).  On the other end of the spectrum, insulin injections destroy energy expenditure.  The former is more likely caused by increased access to fat from adipose to use as fuel, due to chronically lower insulin; whereas the latter is probably due to insulin-induced-hypoglycemia-induced autonomic dysfunction (as previously shown McNay et al., 2006), or impaired sympathetic tone with the opposite net result: less access to fat from adipose to use as fuel.  No.  Matter.  How.  You.  Slice.  The.  Pie.

calories proper

Kindle Edition! –>

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