#29. Fat Loss: Beyond the Basics Monday, August 30, 2021 In last week's blog, we talked about the basics of fat loss. And how sleep, macronutrients, and treadmill behavior influence it. This week, we'll go a little deeper. And discuss climate, micronutrients, and a treadmill alternative. But first, we'll do some nitty-grittying with lipolysis. Remember: this is the mobilization of fat. Lipolysis is step one in its catabolism, i.e., its breakdown... i.e., the burning of your stored fat... i.e., getting bumpier abs. Not "washboard abs" (as the expression goes); no set of cancer-free abdominal muscles has ever resembled a washboard. But challah bread abs? That's what we want to see in the mirror. And effective lipolysis is necessary to get it. So, here's how it works: You have a fat cell. An adipocyte (that's what fat cells are called). This particular adipocyte is in your belly. And its name is Timothy. But it goes by Timmy. But it's considering switching back to "Timothy" so it will be taken more seriously by its colleagues. Timmy, the subcutaneous abdominal adipocyte, is innervated. That means it's on the nervous system's grid. It is physically connected to sympathetic (i.e., adrenal) nerves. These nerves control Timmy and all of his colleagues. How do those nerves make adipocytes initiate lipolysis? They (the sympathetic nerves) release norepinephrine, which is sometimes called noradrenaline. Epinephrine and adrenaline are used interchangeably, just as norepinephrine and noradrenaline are used interchangeably (Aroson, 2000). But epinephrine and norepinephrine are not quite the same thing. Your nerves don't release any epinephrine; they only release norepinephrine. Regular epi comes from your adrenal glands (you have one gland sitting atop of each kidney). Those adrenal glands are also responsible for a little bit of norepi via dopamine, but mostly they release regular epi. In general: sympathetic nerves release norepinephrine (or noradrenaline) and adrenal glands release epinephrine (or adrenaline), and both epi and norepi initiate lipolysis within our adipocytes (Gordan et al., 2015; Bartness et al., 2014; Schmidt et al., 2014). Adipocytes are cells that contain innumerable triglycerides (or triacylglycerols). When epi or norepi binds to a beta-adrenergic receptor on the surface of an adipocyte, a "cell signaling cascade" is activated. Think of cell signaling like a relay race: a starter pistol fires, which commences a series of runners, each passing the baton to the next, one after another, sprinting toward a finish line, until the last runner finally crosses it. In the relay race of lipolysis, the starter pistol fires when epi or norepi binds to a receptor on the surface of an adipocyte. What follows is a series of intracellular events racing toward the finish line: lipolysis. Here's a summary: Epi binds to a beta-adrenergic receptor on Timmy's outer surface. That activates an enzyme called adenylate (or adenylyl) cyclase. Adenylate cyclase converts ATP into cyclic AMP (cAMP). That cAMP binds to an enzyme called protein kinase A (PKA). Then PKA activates the enzymes that are directly responsible for the initiation of lipolysis (Braun et al., 2018). This relay race (cell signaling cascade) can be augmented or inhibited in several ways. Insulin, for example, is the most potent lipolysis-inhibiting hormone in your body. How it enacts its inhibition is multifaceted. Here's one facet: insulin activates an opposing signaling cascade, protein kinase B (PKB), which activates an enzyme called phosphodiesterase (PDE). Once active, PDE converts cAMP into AMP. And AMP, unlike cAMP, does not activate PKA. So PKA doesn't go turn on all of the lipolytic machinery (Zhao et al., 2020). Contrarily, in Blog 26, we talked about NEAT (non-exercise activity thermogenesis). Being a fidgety NEATer triggers lipolysis in Timmy and all of his friends (Levine, 2015; Chung et al., 2018; Kotz et al., 2007). In short, if you want to promote fat loss, then do things that activate lipolysis. And if you want to inhibit fat loss, then do things that deactivate lipolysis. Since this blog is about turning on fat loss, let's tip about lipolysis in an activating way: Tip 1) People attempting to lose weight often find themselves on diets of exclusion. And diets of exclusion often lack key nutrients. For example, someone dieting to reduce blood pressure, may cut salt. But iodized salt may have been that person's primary source of iodine, the thyroid needs iodine, and fat loss needs a healthy thyroid (Tayie et al., 2010). In other words, diets of exclusion sometimes purge wanted nutrients with the unwanted. So, no matter how exclusive your diet becomes, be very careful to maintain the fundamental micronutrients. For your thyroid, avoid deficiencies in iodine (seaweed is best, but also cod, oysters, and eggs) and selenium (moldy Brazil nuts aside, good sources are tuna, halibut, sardines, ham, and shrimp). For glucose regulation and insulin sensitivity, avoid deficiencies in magnesium (pumpkin seeds, chia seeds, almonds, spinach, cashews, black beans) and zinc (shellfish, beef, pork, dark-meaty chicken, pumpkin seeds, cashews, chickpeas). And, for oxygen carrying capacity of the blood, avoid a deficiency in iron (oysters, white beans, dark chocolate, lentils, spinach). Don't consume any of these to excess, but make sure (make sure sure) that they aren't deficient. Because if they are, there's no tip or trick that can compensate. Tip 2) Some people loathe the treadmill. To quote James Hardie, a New York prison guard, it's "the monotonous steadiness" of the treadmill, "and not its severity, which constitutes its terror." That was in 1824... back when treadmills were novel prison technology. They were originally developed in England in 1818 by Sir William Cubitt. At the time, they had a single, broad, rotating paddlewheel, resembling an enormous StairMaster designed for group aerobics classes. Initially, these treadmills were aimed at reforming idle prisoners. Later versions did useful things, such as power grain mills. In a way, their employment was the 19th century equivalent of prisoner squads picking up highway litter. Eventually (i.e., Prisons Act of 1898), the huge torture contraptions were banned. Then, in 1913, a U.S. patent was issued for a treadmill training machine that could reform idle bodies voluntarily. It didn't catch on. Not right away. It wasn't until the 1970s that treadmills began to gain popularity. And here we are today. Some people love them, and others loathe them. If you are of the loathing class, or if you have an acute injury and are looking for a temporary alternative to your usual monotonous steadiness, here is that alternative: go be cold. And make sure you shiver while you're at it. Don't suppress the shivers. In doing so, you'll release lots of things, including epinephrine and norepinephrine (Lee et al., 2014), and you know how those work. But cells also release succinate during shivering, which activates brown fat thermogenesis (Mills et al., 2018). Cold stress can function as an effective substitute for endurance exercise, but don't be crazy about it. It doesn't take frostbite or hypothermia to achieve fat loss. The temperature doesn't have to be arctic and the duration doesn't have to rival cardio. It can just be a bout of interval showering: set the water to unpleasant, then get in and out several times (without drying off). Done correctly (and safely), you can increase fat oxidation and reduce body fat while improving insulin sensitivity and glucose homeostasis (Ivanova et al., 2021). Tip 3) Don't overdo the heat; it's not a good environment for fat oxidation. In part, fat metabolism is highly dependent on oxygen, and oxygen delivery to the metabolically active tissues is less effective while under heat stress (Collins et al., 2015). In addition, excess heat causes carbohydrates to be mobilized in larger amounts while lipolytic enzymes can find themselves impaired. So, while carbs may burn faster in the heat, fat burns better in a cooler flame (Fernandez et al., 2015; Baumgard et al., 2012; Zhao et al., 2018; Starkie et al., 1999; Febbriao et al., 1994).