While we tend to think of excess fat accumulation and poor health as two conditions that go hand in hand, the data actually tells a different story.
While the two tend to correlate when examined with a large enough sample size, there is not a causal relationship between body fat and systemic insulin resistance (1). It turns out that some individuals may be perfectly healthy while carrying around what is generally thought of as excess fat mass. Meanwhile, others may look like a healthy weight from the outside, but actually have significant insulin resistance and metabolic dysfunction.
The important question is why?
What seems to be the important factor is not the amount of stored fat, but the amount of stored fat in relation to the individual’s own fat storage capacity (1).
As long as the cells that make up adipose tissue (adipocytes) can continue to expand and replicate to incorporate more stored fat, then that body will remain healthy (at least from the perspective of this one pathway).
If, however, the adipose tissue cannot take in more energy to store in a healthy manner, then the individual adipocytes (cyte = cell) will become insulin resistant.
When an adipocyte becomes insulin resistant, it will stop taking in energy from the bloodstream and will begin releasing its stored lipids along with a signal for help via a pro-inflammatory, pro-oxidative biochemical cascade.
The result is the build-up of energy-containing molecules (lipids and sugars) in the bloodstream, along with pro-inflammatory, pro-oxidative compounds.
As the bloodstream makes its way through tissues throughout the body, from the perspective of the entire body, this will drive the progression of systemic insulin resistance.
At this point, we could say that the body is in a state of metabolic dysfunction and on its way to the development of clinically relevant symptoms, resulting in the diagnosis of a modern disease (or 2 or 3 or more!)
In summary:
A note from examining the topic further:
Above I focused on the topic of individual adipocyte expansion as the determinant of whether the adipose tissue becomes insulin resistant. This is true in the sense that adipocytes are designed to expand a certain amount, after which point any additional fat accumulation will lead to the biochemical cascade of events that progresses to insulin resistance.
However, when we look at the difference between individuals regarding what exactly it is that enables some individuals to have a higher tolerance for more fat storage, what may be the case is not the individual cell’s ability to expand, but rather, the ability of these cells to replicate (5).
In other words, it’s not a matter of how much fat an individual’s adipocytes can carry, but rather, how capable are an individual’s adipocytes of replicating to take on more fat.
To me, this is interesting, but doesn’t change the point of the matter: when it comes to excess fat accumulation and healthy decisions, it doesn’t help so much to focus on the problem that is accumulating excess fat, but rather, we can create healthier outcomes by thinking about the problem from a different perspective.
Expanding this idea to other sub-systems
Moreover, if you look at fat accumulation within other (non-adipose tissue) tissues or organs, it’s not the presence of fat that determines poor health.
For instance, there is a general trend in the build-up of fat within muscle tissue (intramyocellular triglyceride – IMTG) and insulin resistance. However, if you examine the muscle of endurance athletes, you’ll find that they, too have large fat deposits but do not exhibit the same unhealthy symptoms (inflammation, oxidative stress and insulin resistance) as those in the general population significant amounts of IMTG (4).
So, once again, we can quickly toss out the idea that the build-up of fat is the driver of poor health and instead come up with a better question.
Let’s try: what is driving this cascade of poor health, which includes the build-up of excess fat, inflammation, oxidative stress, and insulin resistance?
References
- Sethi, J. K., & Vidal-puig, A. J. (2007). Adipose tissue function and plasticity orchestrate nutritional adaptation. 48. https://doi.org/10.1194/jlr.R700005-JLR200
- Ertunc, M. E., & Hotamisligil, G. S. (2016). Lipid signaling and lipotoxicity in metaflammation: Indications for metabolic disease pathogenesis and treatment. Journal of Lipid Research, 57(12), 2099–2114. https://doi.org/10.1194/jlr.R066514
- Bosma, M., Kersten, S., Hesselink, M. K. C., & Schrauwen, P. (2012). Re-evaluating lipotoxic triggers in skeletal muscle: Relating intramyocellular lipid metabolism to insulin sensitivity. Progress in Lipid Research, 51(1), 36–49. https://doi.org/10.1016/j.plipres.2011.11.003
- Goodpaster, B. H., J. He, S. Watkins, and D. E. Kelley. 2001. Skeletal muscle lipid content and insulin resistance: evidence for a paradox in endurance-trained athletes. J. Clin. Endocrinol. Metab. 86: 5755–5761.
- Tandon, P., Wafer, R., & Minchin, J. E. N. (2018). Adipose morphology and metabolic disease. https://doi.org/10.1242/jeb.164970