The Skinny on Fat and Covid-19
Obesity is a risk factor for worse outcomes for a variety of medical conditions ranging from cancer to Covid-19. Most experts attribute it simply to underlying low-grade inflammation and added weight that make breathing more difficult.
Now researchers have found a more direct reason: SARS-CoV-2, the virus that causes Covid-19, can infect adipocytes, more commonly known as fat cells, and macrophages, immune cells that are part of the broader matrix of cells that support fat tissue. Stanford University researchers Catherine Blish and Tracey McLaughlin are senior authors of the study.
Most of us think of fat as the spare tire that can accumulate around the middle as we age, but fat also is present closer to most internal organs. McLaughlin's research has focused on epicardial fat, “which sits right on top of the heart with no physical barrier at all,” she says. So if that fat got infected and inflamed, it might directly affect the heart.” That could help explain cardiovascular problems associated with Covid-19 infections.
Looking at tissue taken from autopsy, there was evidence of SARS-CoV-2 virus inside the fat cells as well as surrounding inflammation. In fat cells and immune cells harvested from health humans, infection in the laboratory drove "an inflammatory response, particularly in the macrophages…They secreted proteins that are typically seen in a cytokine storm” where the immune response runs amok with potential life-threatening consequences. This suggests to McLaughlin “that there could be a regional and even a systemic inflammatory response following infection in fat.”
It is easy to see how the airborne SARS-CoV-2 virus infects the nose and lungs, but how does it get into fat tissue? That is a mystery and the source of ample speculation.
The macrophages studied by McLaughlin and Blish were spewing out inflammatory proteins, While the the virus within them was replicating, the new viral particles were not able to replicate within those cells. It was a different story in the fat cells. “When [the virus] gets into the fat cells, it not only replicates, it's a productive infection, which means the resulting viral particles can infect another cell,” including microphages, McLaughlin explains. It seems to be a symbiotic tango of the virus between the two cell types that keeps the cycle going.
It is easy to see how the airborne SARS-CoV-2 virus infects the nose and lungs, but how does it get into fat tissue? That is a mystery and the source of ample speculation.
Macrophages are mobile; they engulf and carry invading pathogens to lymphoid tissue in the lymph nodes, tonsils and elsewhere in the body to alert T cells of the immune system to the pathogen. Perhaps some of them also carry the virus through the bloodstream to more distant tissue.
ACE2 receptors are the means by which SARS-CoV-2 latches on to and enters most cells. They are not thought to be common on fat cells, so initially most researchers thought it unlikely they would become infected.
However, while some cell receptors always sit on the surface of the cell, other receptors are expressed on the surface only under certain conditions. Philipp Scherer, a professor of internal medicine and director of the Touchstone Diabetes Center at the University of Texas Southwestern Medical Center, suggests that, in people who have obesity, “There might be higher levels of dysfunctional [fat cells] that facilitate entry of the virus,” either through transiently expressed ACE2 or other receptors. Inflammatory proteins generated by macrophages might contribute to this process.
Another hypothesis is that viral RNA might be smuggled into fat cells as cargo in small bits of material called extracellular vesicles, or EVs, that can travel between cells. Other researchers have shown that when EVs express ACE2 receptors, they can act as decoys for SARS-CoV-2, where the virus binds to them rather than a cell. These scientists are working to create drugs that mimic this decoy effect as an approach to therapy.
Do fat cells play a role in Long Covid? “Fat cells are a great place to hide. You have all the energy you need and fat cells turn over very slowly; they have a half-life of ten years,” says Scherer. Observational studies suggest that acute Covid-19 can trigger the onset of diabetes especially in people who are overweight, and that patients taking medicines to regulate their diabetes “were actually quite protective” against acute Covid-19. Scherer has funding to study the risks and benefits of those drugs in animal models of Long Covid.
McLaughlin says there are two areas of potential concern with fat tissue and Long Covid. One is that this tissue might serve as a “big reservoir where the virus continues to replicate and is sent out” to other parts of the body. The second is that inflammation due to infected fat cells and macrophages can result in fibrosis or scar tissue forming around organs, inhibiting their function. Once scar tissue forms, the tissue damage becomes more difficult to repair.
Current Covid-19 treatments work by stopping the virus from entering cells through the ACE2 receptor, so they likely would have no effect on virus that uses a different mechanism. That means another approach will have to be developed to complement the treatments we already have. So the best advice McLaughlin can offer today is to keep current on vaccinations and boosters and lose weight to reduce the risk associated with obesity.
How to have a good life, based on the world's longest study of happiness
What makes for a good life? Such a simple question, yet we don't have great answers. Most of us try to figure it out as we go along, and many end up feeling like they never got to the bottom of it.
Shouldn't something so important be approached with more scientific rigor? In 1938, Harvard researchers began a study to fill this gap. Since then, they’ve followed hundreds of people over the course of their lives, hoping to identify which factors are key to long-term satisfaction.
Eighty-five years later, the Harvard Study of Adult Development is still going. And today, its directors, the psychiatrists Bob Waldinger and Marc Shulz, have published a book that pulls together the study’s most important findings. It’s called The Good Life: Lessons from the World’s Longest Scientific Study of Happiness.
In this podcast episode, I talked with Dr. Waldinger about life lessons that we can mine from the Harvard study and his new book.
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More background on the study
Back in the 1930s, the research began with 724 people. Some were first-year Harvard students paying full tuition, others were freshmen who needed financial help, and the rest were 14-year-old boys from inner city Boston – white males only. Fortunately, the study team realized the error of their ways and expanded their sample to include the wives and daughters of the first participants. And Waldinger’s book focuses on the Harvard study findings that can be corroborated by evidence from additional research on the lives of people of different races and other minorities.
The study now includes over 1,300 relatives of the original participants, spanning three generations. Every two years, the participants have sent the researchers a filled-out questionnaire, reporting how their lives are going. At five-year intervals, the research team takes a peek their health records and, every 15 years, the psychologists meet their subjects in-person to check out their appearance and behavior.
But they don’t stop there. No, the researchers factor in multiple blood samples, DNA, images from body scans, and even the donated brains of 25 participants.
Robert Waldinger, director of the Harvard Study of Adult Development.
Katherine Taylor
Dr. Waldinger is Clinical Professor of Psychiatry at Harvard Medical School, in addition to being Director of the Harvard Study of Adult Development. He got his M.D. from Harvard Medical School and has published numerous scientific papers he’s a practicing psychiatrist and psychoanalyst, he teaches Harvard medical students, and since that is clearly not enough to keep him busy, he’s also a Zen priest.
His book is a must-read if you’re looking for scientific evidence on how to design your life for more satisfaction so someday in the future you can look back on it without regret, and this episode was an amazing conversation in which Dr. Waldinger breaks down many of the cliches about the good life, making his advice real and tangible. We also get into what he calls “side-by-side” relationships, personality traits for the good life, and the downsides of being too strict about work-life balance.
Show links
- Bob Waldinger
- Waldinger's book, The Good Life: Lessons from the World's Longest Scientific Study of Happiness
- The Harvard Study of Adult Development
- Waldinger's Ted Talk
- Gallup report finding that people with good friends at work have higher engagement with their jobs
- The link between relationships and well-being
- Those with social connections live longer
The Friday Five: A new blood test to detect Alzheimer's
The Friday Five covers five stories in research that you may have missed this week. There are plenty of controversies and troubling ethical issues in science – and we get into many of them in our online magazine – but this news roundup focuses on scientific creativity and progress to give you a therapeutic dose of inspiration headed into the weekend.
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Here are the promising studies covered in this week's Friday Five:
- A blood test to detect Alzheimer's
- War vets can take their psychologist wherever they go
- Does intermittent fasting affect circadian rhythms?
- A new year's resolution for living longer
- 3-D printed eyes?