Our bodies have complex regulatory mechanisms for food intake and energy expenditure, and the complexity continues to confound scientists seeking to understand these relationships. However, a little over 15 years ago, the discovery of a hormone called leptin, and a growing appreciation for its central role in managing both how much you eat and how much you move, has somewhat clarified the very muddy waters.
Why We Get FatYes, we stole that from Gary Taubes. Taubes, among scores of science writers and actual scientists, has written extensively about the central role that the hormone insulin plays in the storage of body fat. It’s a well-established “fact of life” that insulin functions to let calories (i.e., energy, including carbohydrate and fat) into your cells for immediate usage, and/or storage for future usage. Limited amounts of carbohydrate can be stored in the liver and muscles in a form called glycogen, but it can be converted into an even more “compact” form for longer-term storage: fat.
See, body fat is not a bad thing. It’s what allows us as a species to survive long periods of food shortage. It’s what allows us to not eat for a couple days when we have the flu, and it’s what allows athletes to perform such amazing feats like running from New York to Los Angeles. But our bodies are pessimists. Our DNA always expects, despite the surplus of readily-available energy right now, that food will run out soon, and therefore, the only way to survive this coming famine is… store some energy as fat. It’s as natural as breathing.
But, of course, for those of us in the developed world, there is no famine. Ever. We’ve practically forgotten what it’s like to even be hungry, much less to be actually (temporarily) deprived of food. It almost seems like we (us Westerners) believe we have an inherent right to not be uncomfortable, feel pain, be hungry, or otherwise experience biology’s more unpleasant realities. “Rising above” the realities of nature is a dangerous – and foolhardy – trajectory. But we digress.
As fat is a storage depot for energy, it is important that your body have a way to measure how much fat you have at any given moment, and to control your behavior (primarily, eating and activity) accordingly.
Enter LeptinLeptin is a fascinating, powerful hormone that was only discovered in 1994. As such, the research into leptin’s regulatory role is in its relative infancy. However, there are a few things that we do know:
- A primary function of leptin is to act as a messenger from stored fat to the brain to provide feedback about how much fat is in storage (i.e., the status of our “reservoir” of stored energy). Leptin is secreted into the bloodstream by fat cells (adipocytes) in proportion to the amount of fat mass. More fat, more leptin secreted.
- Leptin also acts as a satiety signal, blocking orexigenic hormones like NPY and AgRP that typically tell us to eat more (and move less). Higher levels of leptin (after meals) register in our brains to say that we’ve eaten enough – for now – and it’s okay to stop eating. Leptin also suppresses ghrelin, another “hunger hormone”. Getting the picture?
- Leptin is structurally and functionally similar to a family of chemical messengers called cytokines. These cytokines – including leptin – regulate important aspects of immunity and inflammation. Leptin can be considered one of the inflammatory (i.e. immune-stimulating) cytokines that fat cells secrete. More fat = more inflammatory cytokines secreted.
- Leptin registers in the brain at the arcuate nucleus of the hypothalamus, a central controller of both appetite and activity level. Key point: in order for leptin to deliver its message, it must register with the appropriate neurons in the hypothalamus. And that doesn’t always happen. [Storm clouds brewing.]
- Leptin, like insulin, is secreted after we eat, and elevated insulin levels cause the secretion of more leptin. Remember which macronutrient tends to drive insulin levels up the most? That’s correct: carbohydrate – particularly energy-dense, nutrient-poor carbohydrate sources like sugar, processed foods, grains and some dairy. Think a highly insulinogenic diet might contribute chronically elevated leptin levels? We do. Interestingly, in normal pancreatic cells, leptin tends to suppress insulin secretion. In the context of a high-carb diet, that could contribute to post-prandial (after eating) periods of prolonged elevated blood glucose. [More storm clouds.]
- Over-consuming food (even temporarily) will create an inflammatory state. This inflammation increases leptin secretion, leading to elevated levels of leptin in the blood (hyperleptinemia). Overeating quickly makes you leptin resistant. Of course, since (over)eating acutely triggers leptin secretion, grazing like an antelope will cause frequent rises in leptin levels. You are a not an antelope. And “all leptin, all the time” is not a good plan.
- Chronically increased leptin levels cause the hypothalamus to become desensitized to the leptin signal, creating leptin resistance, much like other cells can become insulin resistant in the presence of chronically high levels of insulin. Leptin resistance means that the satiety signal is not registering at the brain, which drives ongoing overconsumption of food, and reduces the amount of activity we are inspired to undertake. Furthermore, it turns you into a “sugar burner”, making it difficulty to access body fat for fuel. It also increases the proportion of fat intake that is stored as body fat. It’s like quicksand.
- There is a diurnal rhythm (daily cycle) to leptin secretion, and dysregulation of this pattern can create or exacerbate leptin resistance. (Translation: when you eat matters, too.) For those of you familiar with cortisol’s importance as a stress hormone, you might find this interesting: leptin’s rhythm has pretty much the opposite pattern from normal cortisol secretion, though leptin is tied to when you eat and cortisol is tied to the light/dark cycle. So their patterns are the same, but different.
- Smart people like Robb Wolf have long talked about how elevated cortisol levels will make weight loss incredibly difficult, and that is unequivocably true. However, we believe that the mechanism for this phenomenon is actually via leptin dysfunction. Elevated cortisol in the blood means more leptin is secreted (i.e. hyperleptinemia). More leptin secreted, over time, leads to pancreatic beta cell leptin resistance, so leptin no longer suppresses insulin secretion, leading to blood glucose volatility and likely insulin resistance. [The rain starts.] Worse yet, your hypothalamus becomes leptin resistant, no longer accurately registers how much body fat you have, and tells you to eat all the time, especially at night (since it thinks you’re not fat enough to survive). And… it doesn’t register properly even when you’ve eaten a large meal, so you overeat then, too. [Full-on hurricane.]
Leptin – A Kingpin?So, based on the thousands of leptin studies in the last decade-and-a-half, leptin seems to be a pretty central player in regulation of metabolism. (And don’t think that drug companies don’t want to figure out how to use leptin to treat obesity. They are scrambling to find a way. There’s big money in people being fat – and trying to get unfat.) But all that being said, why are we writing about leptin?
We Think It’s Important
We also think that there is no one “right” reason for why we get fat. Do highly-rewarding foods promote overconsumption? Unquestionably. Do foods that promote chronically elevated insulin levels tend to drive the deposition of body fat? Sure do. Do foods that promote increased gut permeability (and thus inflammation) play a role in leptin resistance and the pathogenesis of obesity? We think so.
But it’s not just food that makes you – or keeps you – fat. Sleep plays an important role, too. And chronic stress is a surefire way to create leptin resistance. (Cortisol potentiates leptin secretion, for those of you who care about the how.) Creating excessive inflammation via over-exercising (or, as we prefer, under-recovering) can further disturb leptin and insulin signaling.
There Is No Easy ButtonWe’re not the only people who view altered leptin signaling as a central problem in the pathogenesis of both obesity and other metabolic conditions, including thyroid dysfunction and some eating disorders. But as central as proper leptin function is, it is not the cure for all your woes. It will not be the “quick fix” to finally getting lean. We observe many trends in our online fitness/health community, and lots of people are writing about leptin these days. But please understand that this is only one aspect of the underlying mechanisms that make each of us healthy… or not as healthy as we could be. It’s not that easy. Sorry. (Yes, we’re #paleobuzzkills.)
In order to optimally integrate all these factors into a life that is healthier in the future than it was in the past, you have to address all the components. Unfortunately, simply eating a healthy Paleo-ish diet and exercising smarter-not-harder cannot undo all the damage that your old habits caused. The route from B to A is not always the same as it was from A to B.