The Food Combo That Makes You Fat

Brain Chemistry, Metabolic Regulation and Cravings

It’s About More Than Calories

We all know that eating too many calories and burning too few of them make you gain weight. But if that’s all there is to getting fat, why do sleep deprivation and chronic stress have such an impact on fat gain?

These things don’t have calories, and you can’t eat them, yet they impact whether we store fat or burn it. They also dramatically affect our hunger, motivation to workout, and cravings.

So while it’s true that calorie excess is required to gain weight, just as calorie deficits are required to lose it, this is shortsighted. The body is a highly complex biochemical machine, not a simple math equation.

It’s About More Than Willpower

The assumption that all overweight people are lazy gluttons is insulting. It’s ignorant to assume that anyone not getting results from diet and exercise is simply not being “compliant.” Or those who are unable to control their eating are simply gluttons with no willpower who just need to be yelled at.

When you really begin to look into the question, “What makes us gain weight?” you find it’s a bit more complex than the “eat less, exercise more” model leads us to believe.

Fat gain and weight loss is multi-factorial and specific. It involves understanding individual genetics, unique metabolic expression, psychological sensitivities, and even personal preferences. However, there does appear to be some overarching themes.

The Fat Gain Formula

Want to know the fat gain formula? Here it is:

  • (F + S) x St = Fat Gain

High fat (F) along with high sugar (S) combined with stress (St) is the recipe for fat gain.

I can hear the calorie zealots now scoffing at the ridiculousness of this assertion. Sure, you can get fat overeating anything, including broccoli and chicken breasts… except that it’s virtually impossible for any living human to do.

A high fat/sugar combination has been shown in mammals to completely disrupt the normal metabolic regulation that occurs with either high fat or high sugar diets. So, this combo is not only a higher calorie diet, but it seems to have the impact of assuring we continue to crave high fat, high sugar foods in the future as well.

The combo alters brain chemistry in a way that disrupts the natural ability to self-regulate calorie intake.

Fat and Sugar

Fat + Sugar = Willpower Sabotage

Here’s how it works: You have a control center for appetite in your brain that resides in the hypothalamus. There are chemicals that stimulate eating: Neuropeptide Y (NPY) and Agouti related peptide (AGRP). And there’s a chemical that suppresses food intake: Proopiomelanocortin (POMC).

Think of NPY and AGRP as feeding gas pedals. They make us hungry and make us eat. Think of POMC as the brakes on food intake. If you’re wondering how hunger hormones like ghrelin and leptin figure into this, they work by impacting these chemicals.

Two diets containing the same number of calories can impact these hunger regulation chemicals differently. Fat and sugar in combination short-circuit the hunger centers, resulting in a constant desire for food.

It’s Like An Appetite Stimulating Drug

A study published in the International Journal of Obesity looked at this issue in rats. The animals were fed a base diet of healthy rat chow. They were then given free access to extra fat, extra sugar, or extra fat and sugar.

Imagine you were a part of a study where the researchers gave you a normal healthy diet, but then put you in a group that had free access to bacon, cream cheese, and other high fat items. That’s the high fat group.

Or perhaps you end up in the group that got the healthy diet with additional access to cotton candy, Coca-Cola, and other high sugar, no fat items. That’s the high sugar group.

Or maybe you got to be in the high fat and high sugar group, receiving a normal healthy diet plus cupboards stacked with cookies, cakes, pastries, ice cream, and other foods loaded with BOTH fat and sugar, which you could eat freely. That’s obviously the high fat, high sugar combo group.

So, what do you think happened? Well, the rats exposed to all-you-can-eat palatable foods did what we humans do: they ate the normal rat chow and then chowed down on the fat and sugar items.

All three groups consumed extra calories and gained weight. But within a week or so, two groups, the high fat and high sugar groups, were able to self-regulate their food intake, lower their calories, and adapt by shutting off hunger.

This natural adaptation did NOT occur with the high fat and high sugar combination group. In other words, eating a high fat, high sugar diet caused a loss in the ability to properly regulate appetite, almost like an appetite stimulating drug.

The researchers noticed that the high fat group and the fat/sugar combo group had the exact same hormone response from the diets (i.e. leptin, a hunger hormone, had the same response). This caused the researchers to look for other hormones or nerve signals that may have caused this. What they discovered is that something about the high fat, high sugar diet was being communicated to the brain via the gut and liver.

6 Pounds of Fat in 7 Days

Studies show humans, who are isolated in a metabolic chamber and given free access to highly palatable foods, do what the rats do: they overeat by huge margins.

The participants in these studies end up eating close to a 1,000-calorie surplus, and gain, on average, 6 pounds in only 7 days. While the metabolism does ramp up its calorie burn as well, you can see something very detrimental happens when these types of junk foods are chosen. There are several other studies that show a similar effect.


The Stress Factor

There’s one more very interesting piece to this story. Remember, we talked about the fat storing formula as being (F+S) X St or fat combined with sugar magnified by stress. Stress is like the cherry on top of the fat-storing, hot fudge sundae.

When you think stress, you probably think cortisol. If you’re really savvy, you’ll also think catecholamines. If you’re really, really savvy, there’s one more hormone you think about: NPY.

NPY is involved with hunger in the brain, and it’s also released from the sympathetic nervous system during times of stress. When under acute stress, we release more of the catecholamines and cortisol. When we’re under chronic stress we release more NPY.

And, unlike the catecholamines and cortisol, which are mainly catabolic hormones (i.e. they burn fat), NPY makes you gain fat, especially when it’s around cortisol. When NPY is released in large amounts, it causes fat cells to go from immature baby fat cells to full-grown, mature fat cells. And cortisol makes the body more responsive to NPY. In other words, NPY makes us grow more fat cells and cortisol enhances its efficiency to do so.

Confused? Let me restate it:

  • Chronic, continuous stress releases a unique mix of NPY and cortisol.
  • Cortisol combined with catecholamines, like it is in short-term stress, helps us burn fat.
  • Cortisol combined with NPY, as it is in chronic stress, equals increased fat cells.

Another interesting aside: Even when you feed mice high amounts of fat and sugar, obesity is not guaranteed. But, add stress on top and BOOM, it seems you can induce obesity very easily.

One final note on the stress weight gain response: Low calorie diets increase cortisol levels and perceived psychological stress. Some researchers believe this is one of the key reasons low calorie diets fail.

A Formula for Disaster

If you read all this carefully, you’ll notice a couple of interesting things. A high fat diet with the same number of calories as a high fat/high sugar diet has a very different impact on metabolism.

The metabolism adapts to the extra calories in a high fat diet by decreasing appetite so that, after a few weeks, the calories are no longer high. This explains why studies on the high fat Atkin’s diet usually show a low calorie, not high calorie, intake over time. The metabolism adapts.

The high fat and sugar combination creates the exact opposite changes in the hunger-signaling molecules in the brain and results in insatiable hunger that continues. Ironically, this change is almost exactly the pattern seen in starvation.

We can see that high fat, high sugar foods aren’t just simply high calorie, but they also cause us to lose our ability to regulate and suppress hunger. They cause hyperphagia (the fancy medical term for continuous eating). And, when we add chronic stress on top of this, we create the perfect fat-storing atomic bomb.

The solution? Well, obviously, don’t follow the fat gain formula.


  1. la Fleur et al. A free-choice high-fat high-sugar diet induces changes in arcuate neuropeptide expression that support hyperphagia. Int J Obes (Lond). 2010 Mar;34(3):537-46. doi: 10.1038/ijo.2009.257. Epub 2009 Dec 22.
  2. Rising et al. Food intake measured by an automated food-selection system: relationship to energy expenditure. Am J Clin Nutr. 1992 Feb;55(2):343-9.
  3. Larson et al. Spontaneous overfeeding with a ‘cafeteria diet’ in men: effects on 24-hour energy expenditure and substrate oxidation. Int J Obes Relat Metab Disord. 1995 May;19(5):331-7.
  4. Larson et al. Ad libitum food intake on a “cafeteria diet” in Native American women: relations with body composition and 24-h energy expenditure. Am J Clin Nutr. 1995 Nov;62(5):911-7.
  5. Brante P. Sampey, Published online 2011 Feb 17. doi: 10.1038/oby.2011.18
  6. PMCID: PMC3130193. Cafeteria Diet Is a Robust Model of Human Metabolic Syndrome With Liver and Adipose Inflammation: Comparison to High-Fat Diet Obesity (Silver Spring). 2011 Jun; 19(6): 1109–1117.
  7. Lydia E. Kuo, Chronic Stress, Combined with a High-Fat/High-Sugar Diet, Shifts Sympathetic Signaling toward Neuropeptide Y and Leads to Obesity and the Metabolic Syndrome. Ann N Y Acad Sci. 2008 Dec; 1148: 232–237.
  8. doi: 10.1196/annals.1410.035 PMCID: PMC2914537
  9. NIHMSID: NIHMS184052
  10. A. Janet Tomiyama, Ph.D. Low Calorie Dieting Increases Cortisol. Psychosom Med. 2010 May; 72(4): 357–364. doi 10.1097/PSY.0b013e3181d9523c
  11. NIHMSID: NIHMS198826
  12. Banasik, et al. Low-calorie diet induced weight loss may alter regulatory hormones and contribute to rebound visceral adiposity in obese persons with a family history of type-2 diabetes. J Am Assoc Nurse Pract. 2013 Aug;25(8):440-8. doi: 10.1111/j.1745-7599.2012.00808.x. Epub 2012 Nov 20.
  13. Gary D. Foster, PhD, et aql. Weight and Metabolic Outcomes After 2 Years on a Low-Carbohydrate Versus Low-Fat Diet: A Randomized Trial. Annals of Internal Medicine.