Cancer Cachexia: Might This Molecule Hold the Key?

PTHrP

Caption: Structure of parathyroid hormone-related protein (PTHrP), which has been implicated in cancer-related cachexia.
Source: The Protein Data Bank

No matter how much high-calorie food they eat or nutritionally fortified shakes they drink, many people with cancer just can’t seem to maintain their body weight. They lose muscle and fat, sometimes becoming so weak that they can’t tolerate further treatment. Called cachexia, this progressive wasting syndrome has long troubled patients and their families, as well as baffled scientists searching for ways to treat or perhaps even prevent it.

Some previous studies [1-3] have observed that humans and mice suffering from cachexia have “activated” brown fat. This type of fat, as I explained in a previous post, has the ability to convert its chemical energy into heat to keep the body warm. Intrigued by these hints, a team led by Bruce Spiegelman of the Dana-Farber Cancer Institute and Harvard Medical School in Boston recently decided to explore whether tumor cells might secrete molecules that spur similar brown fat-like activity, causing a gradual depletion of the body’s energy stores.

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Fighting Obesity: New Hopes From Brown Fat

Artist rendition of a xray showing brown fat as glowing green

Caption: Brown fat—actually marked in green on this image—is wrapped around the neck and shoulders. This “shawl” of brown fat warms blood before it travels to the brain.
Illustration: John MacNeill, based on patient imaging software designed by Ilan Tal. Copyright 2011 Joslin Diabetes Center

If you want to lose weight, then you actually want more fat, not less. But you need the right kind: brown fat. This special type of fatty tissue burns calories, puts out heat like a furnace, and helps to keep you trim. White fat, on the other hand, stores extra calories and makes you, well, fat. Wouldn’t it be nice if we could instruct our bodies to make more brown fat, and less white fat? Well, NIH-funded researchers have just taken another step in that direction [1].

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Brown Fat, White Fat, Good Fat, Bad Fat

Photo of adipocytes in white adipose

Caption: Brown fat cells (stained brown with antibodies against the brown fat-specific protein Ucp1) nestled in amongst white fat cells.
Credit: Patrick Seale, University of Pennsylvania School of Medicine

Fat has been villainized; but all fat was not created equal. Our two main types of fat—brown and white—play different roles. Now, two teams of NIH-funded researchers have enriched our understanding of adipose tissue. The first team discovered the genetic switch that triggers the development of brown fat [1], and the second figured out how the body can recruit white fat and transform it into brown [2].

Why would we want to change white fat into brown? White fat stores energy as large fat droplets, while brown fat has much smaller droplets and is specialized to burn them, yielding heat. Brown fat cells are packed with energy generating powerhouses called mitochondria that contain iron—which gives them their brown color. Infants are born with rich stores of brown fat (about 5% of total body mass) on the upper spine and shoulders to keep them warm. It used to be thought that brown fat disappeared by adulthood—but it turns out we harbor small reserves in our shoulders and neck. Continue reading