It is my opinion that there are as many roads to obesity as there are obese people. However, they all start with excessive eating and decreased physical activity.
What Will You Read Here?
7 Causes of Obesity
I am of the opinion that several additional factors accelerate or exacerbate the road from lean to obese. Namely:
1. Over consumption of refined carbohydrates.
2. Over consumption of fructose.
3. Over consumption of grains at the expense of vegetables.
4. Imbalanced omega-6 to omega-3 fatty acid intake.
5. Over consumption of all fatty acids.
6. Overuse of stimulants.
7. Over consumption of sodium.
As I stated before there are numerous ways to become overweight, though it all generally starts with fat cell hypertrophy or elevated blood pressure. I stated previously that several factors are most likely to blame for America’s current obesity epidemic in addition to the obvious culprit, excessive caloric consumption. These factors are:
Over Consumption of Refined Carbohydrate Sources
In the modern world we eat far too much refined starch and sugar. Ideally what type of carbohydrates we consume should not matter. Refined carbohydrates elicit a large increase in plasma insulin levels, however. This drives blood glucose too low and serves to increase hunger shortly after eating. For our ancestors this was not a problem, as they could not simply open the cupboard when they became hungry. For you and me this is a serious issue. It results in excessive caloric consumption with a reduced sense of fullness. Refined carbohydrates are also digested much more quickly. This increases firing of the vagal nerve to the medulla oblongata, which ultimately leads to a lowered estrogen setpoint, reduced testosterone levels, as well as elevated cortisol release.
Over Consumption of Fructose
Fructose is an odd carbohydrate. It is really only usable by your liver as it requires GLUT5 for transport into cells. Fructose is essentially the opposite of refined starches as described above. Because of the special way in which fructose is metabolized it skips the rate-limiting step of PFK-1. Because of this it oxidizes in the liver incredibly quickly and tricks your liver in to thinking you have plenty of glucose even if you don’t. This affects the hepatic glucose sensor described previously. It causes increased GABA delivery to the PVN, thus slowing metabolism. It can induce hyperglycemia (our arch nemesis) by interactions with several systems. As stated, it reduces PVN firing so that means less thyroid, cortisol, and NE release.
More importantly, fructose is non-insuligenic. Because of this it does not stimulate leptin or alpha-MSH production. So the LH in your brain never deciphers that the body is being fed. The third problem with fructose is that it fails to activate the portal vein glucose sensor, and thus it does not activate this essential glucose disposal mechanism. So in summation, fructose: slows metabolism, lowers leptin, fails to decrease hunger, and causes hyperglycemia. All in all too much fructose is just plain bad. Keep in mind a little fructose can be good, especially if you are an athlete. However for someone that is almost never glycogen depleted, fructose is detrimental and only does harm (1).
Over Consumption of Grains at the Expense of Vegetables
Over consumption of grains at the expense of fibrous vegetables causes two problems. First, to a lesser extent, the arguments given for refined carbohydrates apply to grains as well—at least when compared to vegetables. High yield grain agriculture is a relatively recent advancement in evolutionary terms. Put rather simply we were never meant to eat this much grain. Secondly, grain consumption at the expense of vegetables can result in low-grade metabolic acidosis (2). This has a bad effect on GH and insulin sensitivity as well as bone and muscle anabolism.
Finally it can exacerbate the problems associated with excess fat consumption. The rate-limiting enzyme in fat oxidation is CPT. CPT is extremely sensitive to pH (3). The small reduction in pH seen during exercise completely deactivates CPT. This is why you tend to burn glucose exclusively during high intensity exercise. So, chronic sub-clinical metabolic acidosis can result in attenuated fatty acid oxidation. The result: more dietary fat is stored instead of utilized as fuel.
Omega-3 Fatty Acid Deficiency
Omega-3 fatty acids have so many diverse effects that I can’t hope to touch on them all in this article. However I will attempt to highlight the key points that are not often discussed. First and foremost omega-3 fatty acids need to be a constant part of one’s diet. This is because omega-3 fatty acids are preferentially released by adipose tissue during lipolysis. Thus over time most of the fat stored in your fat cells tends to be of the saturated, monounsaturated, and omega-6/9 polyunsaturated fatty acids.
In our modern diets we tend to pick and choose which parts of animals we eat and we tend not to eat the same thing everyday. Our ancestors did not have such luxury. So even when we eat the occasional meal rich in omega-3 fatty acids it is not of tremendous benefit. Unless consumption is chronic, as in everyday usage, it can be difficult to maintain omega-3 fatty acid stores.
Secondly, DHA deficiency reduces BBB transport of glucose and also lowers KIR neuronal sensing of glucose. The last thing we want is deregulated brain glucose control, as it just makes all the systems so unstable. Rats that were purposefully given DHA deficient diets showed lower levels of GLUT3 protein in neurons. GLUT3 is the transporter that moves glucose in to neurons. Thus DHA deficiency can make the brain look resemble that of an obese person’s (4).
Overuse of Stimulants
Overuse of caffeine and other stimulants has negative long-term ramifications for body composition. Caffeine elevates cAMP, which activates AMPK in skeletal muscle. This is one way it aids in fat burning. However, AMPK also lowers cellular metabolism in the long run, reducing your energy requirements and slowing your metabolism. AMPK is basically a cellular brake; it is activated by the endocrine system during the hypoglycemic state. This serves to switch the cell to fat usage to preserve glucose for the brain. It also reduces the cell’s metabolism however, thus saving any blood glucose for the brain as well.
Secondly, caffeine exhibits some nasty effects brought about by being an adenosine antagonist. Caffeine reduces cell volume by acting as a cellular diuretic. Cell volume is intimately tied to anabolism. In fact it has been proposed that the majority of insulin’s anabolic action is exerted through increases in cell volume. Adenosine antagonist’s also induce insulin resistance, and cause one to spend more time each day in the hyperglycemic state.
Finally, caffeine interferes with the conversion of omega-3 fatty acids into EPA and DHA, thus emulating some of the negative aspects of omega-3 deficiency.
Overuse of ephedrine and other NE promoters is also counterproductive. As discussed above, NE activation in the PVN leads to long-term changes in the PVN that favor CRF over TRH. This both reduces metabolism and lowers sex hormones, resulting in decreased anabolism and increased muscle loss.
Over Consumption of Sodium
Too much sodium has been implicated in accelerating obesity in those who are already prone to it. It is likely this occurs through several distinct mechanisms, the primary ones being increased blood pressure and increased renal re-absorption of glucose. Both of these conditions lead to elevated blood glucose levels.
Sodium’s effect in this regard can be seen in an interesting study on Sprague-Dawley rats. These rats are basically normal. If overfed, about half of the rats get fat and about half don’t—much like people. The authors decided to see what effect increased salt intake would have on those that are prone to obesity. Salt increased the size and reduced the number of adipocytes; in other words, it created hypertrophied fat cells as described earlier. The salt fed rats also had double the leptin levels of their non salt-fed counterparts. Thus sodium seems to accelerate the endocrine system’s adaptations to obesity (5).
Concluding: Causes of Obesity
I hope you enjoy this culminating piece in the leptin series. In the future, I plan to apply the above model to the different human phenotypes so that I can offer more practical advice for use in the real world. After all, this science stuff is fun, but in the end we’re all just interested in putting on some muscle and losing some fat.
References for 'Causes of Obesity'
(1) Elliott SS, Keim NL, Stern JS, Teff K, Havel PJ. Fructose, weight gain, and the insulin resistance syndrome. Am J Clin Nutr. 2002 Nov;76(5):911-22. doi: 10.1093/ajcn/76.5.911. PMID: 12399260.
(2) Anthony Sebastian, Lynda A Frassetto, Deborah E Sellmeyer, Renée L Merriam, R Curtis Morris, Jr, Estimation of the net acid load of the diet of ancestral preagricultural Homo sapiens and their hominid ancestors, The American Journal of Clinical Nutrition, Volume 76, Issue 6, December 2002, Pages 1308–1316, https://doi.org/10.1093/ajcn/76.6.1308
(3) Jeukendrup AE. Regulation of fat metabolism in skeletal muscle. Ann N Y Acad Sci. 2002 Jun;967:217-35. doi: 10.1111/j.1749-6632.2002.tb04278.x. PMID: 12079850.
(4) Ximenes da Silva A, Lavialle F, Gendrot G, Guesnet P, Alessandri JM, Lavialle M. Glucose transport and utilization are altered in the brain of rats deficient in n-3 polyunsaturated fatty acids. J Neurochem. 2002 Jun;81(6):1328-37. doi: 10.1046/j.1471-4159.2002.00932.x. PMID: 12068080.
(5) Dobrian AD, Schriver SD, Lynch T, Prewitt RL. Effect of salt on hypertension and oxidative stress in a rat model of diet-induced obesity. Am J Physiol Renal Physiol. 2003 Oct;285(4):F619-28. doi: 10.1152/ajprenal.00388.2002. Epub 2003 Jun 10. PMID: 12799306.