More Complicated Than It Looks: Complications of Metabolism

by Jennifer Thompson, MPH

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If you ever dare to venture into the comments section of any article about weight, weight loss, obesity, exercise or health, eventually you’ll find someone who says some version of the following: “All people have to do is eat less and exercise more, and they’ll lose weight.”  In a broad sense, this is true; calories are energy, and our bodies use that energy to fuel our basic bodily functions, like circulation, respiration, digestion, and physical activity.  Excess calories are stored by the body as fat.  Yet it also grossly oversimplifies the complexity of our metabolisms.

A recent article in the New York Times had the provocative title “Skinny and 119 Pounds, but With the Health Hallmarks of Obesity.”  It described the case of Claire Walker Johnson, a woman who could and did eat whatever she wanted without gaining weight. Yet despite having a Body Mass Index of 18.6 kg/m2, considered borderline underweight, Ms. Johnson had many of the health conditions commonly associated with obesity, including fatty liver disease; ovarian cysts; high blood pressure, cholesterol and triglycerides; and Type 2 diabetes. Her baffled doctor searched for years for the cause of her contradictory health conditions and eventually learned of a rare genetic condition called lipodystrophy. 

Patients with lipodystrophy have abnormally low levels of fatty tissue in their bodies. Ms. Johnson’s lack of fatty tissue triggered a vicious metabolic cycle; with too little stored body fat, her brain received too little of a hormone called leptin, which is produced by fat cells and, among other things, regulates satiety, or fullness. Her brain registered her low levels of leptin and body fat, concluded that she was starving, and commanded her to eat. And yet she was unable to store the excess calories she consumed as normal fatty tissue. Instead, the fat accumulated in her liver and remained circulating in her blood.  When she participated in a clinical trial of a synthetic version of leptin, her liver recovered and her blood glucose and cholesterol levels dropped to normal levels. As mentioned, metabolism is complex, and Ms. Johnson is the perfect case of a rare condition that leads to very atypical patterns.

Another recent, high-profile study highlighted the metabolic consequences of major weight loss among another rarified group – participants on the reality television show The Biggest Loser.  The show challenges contestants to see who can lose the most weight. The winner receives a huge cash prize. Over the years of this show, many participants have demonstrated an enormous amount of weight loss. Danny Cahill, the winner of season 8, lost 239 pounds over 7 months, or more than half of his baseline body weight of 430 pounds. Yet when NIH researchers conducted a study of Cahill and some of his fellow competitors 6 years later, they found that most, including Cahill, had regained at least some of the weight they had lost.  They also found that contestants’ resting metabolic rates (RMRs), the number of calories their bodies needed for basic biological functions and to maintain their weight, were unexpectedly low.  To a degree, RMR reflects weight. People with overweight and obesity tend to require more daily calories than those who weigh less, and the RMR declines with weight loss. What makes this such a challenge is that the decline in RMR may be disproportionate to the weight lost. In other words, a person who weighed 200 pounds and lost 50 typically has a lower resting metabolic rate than someone who has maintained a steady weight of 150 pounds.  In Danny Cahill’s case, they found that he required 800 fewer calories per day than expected at his current weight of 295 pounds.  While the precise mechanism of this metabolic slowdown is unclear, the same researchers found an association between low levels of leptin and lower RMR in an earlier study, also involving Biggest Loser contestants. This makes maintaining weight loss very, very difficult.

My point isn’t that it’s impossible for anyone to lose weight, or that we’re simply at the mercy of our hormones and metabolisms. One of my favorite quotations, however, is “be kind, for everyone you meet is fighting a hard battle.”  Weight loss is ultimately far more complicated than “eat less and exercise more,” involving many different factors, and the stranger on the street – or in the internet comments section – may be working harder than you realize to gain, maintain, or lose weight.