{"id":63576,"date":"2022-04-20T10:25:48","date_gmt":"2022-04-20T16:25:48","guid":{"rendered":"https:\/\/www.uchealth.org\/today\/?p=63576"},"modified":"2025-03-03T12:57:17","modified_gmt":"2025-03-03T19:57:17","slug":"why-we-gain-weight-nature-may-want-us-to-be-fat","status":"publish","type":"post","link":"https:\/\/www.uchealth.org\/today\/why-we-gain-weight-nature-may-want-us-to-be-fat\/","title":{"rendered":"Why we gain weight. Nature may want us to be overweight, but you don’t have to agree"},"content":{"rendered":"
<\/div>
\"A
Dr. Richard Johnson\u2019s work, described in his latest book, Nature Wants Us to Be Fat, implicates fructose \u2013 and salt, and umami \u2013 in our propensity to put on weight. Photo: Getty Images.<\/figcaption><\/figure>\n

Dr. Richard Johnson<\/a>\u2019s research on the effects of fructose on lab mice has grown into what may just become a unified theory of human obesity.<\/p>\n

Johnson, a University of Colorado School of Medicine kidney specialist who sees patients at the UCHealth Kidney Disease and Hypertension Clinic – Anschutz Medical Campus<\/a>, has brought those who haven\u2019t kept up with his team\u2019s peer-reviewed research and related science up to date in his wide-ranging and readable new book, Nature Wants Us to Be Fat<\/em><\/a>: The Surprising Science Behind Why We Gain Weight and How We Can Prevent \u2013 and Reverse \u2013 It<\/em> (BenBella Books).<\/p>\n

The story includes findings familiar from Johnson\u2019s last book on the topic, The Fat Switch<\/em><\/a>, published in 2012. Then, based largely on his group\u2019s work over the past decade, he expands upon them. Some of the conclusions are unsettling; fortunately, Nature Wants Us to Be Fat<\/em> also includes suggestions about what we can do to overcome our biologically rooted propensity to put on pounds.<\/p>\n

The familiar findings are that fructose \u2013 a type of sugar common in many fruits, a component of table sugar, and the main player in the high fructose corn syrup that sweetens soft drinks and so many processed foods \u2013 triggers a cascade of changes inside of cells that instruct the body to burn less fuel and instead convert it to fat. Johnson calls this trigger a \u201csurvival switch.\u201d The switch brings about \u201ca whole series of physical and metabolic changes, as well as behaviors, that protect animals in nature when food is not available.\u201d<\/p>\n

\"Dr.
Dr. Richard Johnson<\/figcaption><\/figure>\n

Mutations that mattered<\/strong><\/h2>\n

The human body also harbors this switch, and it\u2019s causing big problems: Today, more than 40%<\/a> of U.S. adults are obese. That\u2019s because, when food isn\u2019t scarce, the survival switch becomes a \u201cfat switch,\u201d Johnson says, driving obesity that then triggers metabolic syndrome<\/a> and some of our most pernicious health problems: among them heart disease, diabetes, and high blood pressure \u2013 which often damages the kidneys Johnson specializes in treating.<\/p>\n

Why? Johnson cites his own group\u2019s work and that of others as well as lessons from nature, history, and evolution. His examples from nature are wide-ranging. The emperor penguin, the thirteen-lined ground squirrel, the pacu fish, hummingbirds, and the fat-tailed dwarf lemur count among many other creatures that get fat so they can then fast (in the hummingbird\u2019s case, its hotrod metabolism means not eating overnight qualifies as a fast).<\/p>\n

The key examples from human history and evolution hinge largely on one mutation genomically traced back to before the Chicxulub<\/a> impact that ended the reign of the dinosaurs about 65 million years ago, and a second mutation dating back about 15 million years. The first erased our ancestors\u2019 ability to produce vitamin C. The second made us make more uric acid than other primates by inactivating an enzyme called uricase. The net effect of these mutations is that the prehuman creatures that ended up with them added fat more easily than those that didn\u2019t, and that fat helped them survive.<\/p>\n

Many triggers contribute to weight gain<\/strong><\/h2>\n

How does the survival switch work? Mice given lots of fructose end up turning some of it into uric acid (most famous for causing gout) rather than burning it off. The uric acid then creates oxidative stress in a cell\u2019s mitochondria (energy-factory organelles), which then triggers weight gain that can become harder and harder to reverse as mitochondria get degraded from years of uric-acid baths. That\u2019s where we more or less left off in 2012.<\/p>\n

As Johnson\u2019s new book makes clear, subsequent research has shown that the above narrative is only part of the story. It turns out that the body can make its own fructose through something called the polyol pathway. That means the obvious solution \u2013 cutting back on fructose alone \u2013 won\u2019t necessarily duct tape the survival-switch-turned-fat-switch in the off position. Glucose, Johnson and longtime collaborator Miguel Lanaspa found, can also trigger the fat switch. Hence Johnson\u2019s advice to avoid carbohydrates with a high glycemic index<\/a> (they probably include many of your favorites).<\/p>\n

Additional studies with mice found that a high-salt diet can also trigger the polyol pathway of fructose-to-fat production through dehydration (fat stores water for future use \u2013 hence the camel\u2019s hump). That process is probably set about by fructose\u2019s leading to more production of vasopressin, a hormone that regulates blood pressure by managing the body\u2019s fluid levels, Johnson says.<\/p>\n

\"A
Dr. Richard Johnson’s latest book, Nature Wants Us to Be Fat explores the science behind why we gain weight and how we can prevent \u2013 and reverse – it. Photo courtesy Dr. Richard Johnson<\/figcaption><\/figure>\n

Johnson and Lanaspa also found that foods high in umami \u2013 the rich, savory flavor our taste buds detect alongside salty, sweet, sour, and bitter \u2013 kick off the polyol pathway to fructose production. Beer, high in umami thanks to the yeast that helps make it beer, can be a particular culprit, he says \u2013 not to mention that alcohol itself can kick off fructose production and trigger the survival switch.<\/p>\n

So: what to do? Johnson notes that low-carb, ketogenic, and intermittent-fasting diets all happen to have fructose-limiting features. Johnson is a fan of the Mediterranean diet<\/a>. In the book, he offers up ideas under the rubric \u201cThe Switch Diet.\u201d Among other ideas, it suggests avoiding soft drinks and fruit juices, taking 500 milligrams of vitamin C daily (an antioxidant that reduces the oxidative impact of uric acid on the mitochondria), drinking coffee (ditto), eating dark chocolate (contains epicatechin, also a strong antioxidant), watching salt intake and drinking six to eight glasses of water a day (to cut the risk of dehydration-driven fructose production), and laying off beer and red meat (they\u2019re umami-rich).<\/p>\n

It turns out that Johnson\u2019s ideas on what constitutes a healthy diet, derived from such activities as observing the cellular habits of lab mice and contemplating prehuman ancestors\u2019 seasonal gorging on figs (they\u2019re really high in fructose), are much the same as those of<\/a> Tufts professor Dariush Mozaffarian<\/a>. And finally, exercising to stimulate mitochondrial activity and growth is a good idea, Johnson says, pointing to the work of CU School of Medicine and exercise-science pioneer Inigo San Millan<\/a>.<\/p>\n

Of course, there are other theories as far as why we\u2019re collectively fat. Two leading ones have to do with energy balance (calories in minus calories out equals fat) and carbohydrates causing obesity by stimulating insulin, which drives fat production. Neither are incompatible with Johnson\u2019s survival-switch hypothesis, he says.<\/p>\n

\u201cIt\u2019s a matter of what initiates and what perpetrates,\u201d he said.<\/p>\n

The survival switch, in his mind, initiates for many perpetrators, and those perpetrators are causing a health crisis. He makes clear that, as a scientist, he\u2019s only following where the data lead. The last decade has brought little to dent his survival-switch hypothesis, and his ideas and peer-reviewed conclusions have gained prominent adherents<\/a>. The pharmaceutical industry\u2019s interest<\/a> in drugs that might inhibit fructose\u2019s ability to activate the switch underscores that.<\/p>\n

Johnson, 68, figures he\u2019ll be long gone by the time human trials definitively prove him right or wrong. While his own research program may be winding down, he collaborates with labs in Turkey, Mexico, Korea, and elsewhere, usually helping shape research strategies. He\u2019s still treating patients at UCHealth University of Colorado Hospital.<\/p>\n

\u201cIt fuels my desire, keeps me homed-in, and fuels my curiosity, interest and passion,\u201d Johnson said. \u201cWhen you see how people are suffering from a disease, it really is a great stimulus to try and find ways to cure it.\u201d<\/p>\n","protected":false},"excerpt":{"rendered":"

Dr. Richard Johnson\u2019s research on the effects of fructose on lab mice has grown into what may just become a unified theory of human obesity. Johnson, a University of Colorado School of Medicine kidney specialist who sees patients at the UCHealth Kidney Disease and Hypertension Clinic – Anschutz Medical Campus, has brought those who haven\u2019t […]<\/p>\n","protected":false},"author":23,"featured_media":63580,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_relevanssi_hide_post":"","_relevanssi_hide_content":"","_relevanssi_pin_for_all":"","_relevanssi_pin_keywords":"","_relevanssi_unpin_keywords":"","_relevanssi_related_keywords":"","_relevanssi_related_include_ids":"","_relevanssi_related_exclude_ids":"","_relevanssi_related_no_append":"","_relevanssi_related_not_related":"","_relevanssi_related_posts":"","_relevanssi_noindex_reason":"","footnotes":""},"categories":[6],"tags":[280,9187,551],"class_list":["post-63576","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-healthy-living","tag-kidney-disease-hypertension","tag-readysetco","tag-weight-and-metabolism"],"acf":[],"yoast_head":"\nWhy we gain weight. 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Nature may want us to be overweight, but you don’t have to agree"}]},{"@type":"WebSite","@id":"https:\/\/www.uchealth.org\/today\/#website","url":"https:\/\/www.uchealth.org\/today\/","name":"UCHealth Today","description":"UCHealth Today","publisher":{"@id":"https:\/\/www.uchealth.org\/today\/#organization"},"potentialAction":[{"@type":"SearchAction","target":{"@type":"EntryPoint","urlTemplate":"https:\/\/www.uchealth.org\/today\/?s={search_term_string}"},"query-input":{"@type":"PropertyValueSpecification","valueRequired":true,"valueName":"search_term_string"}}],"inLanguage":"en-US"},{"@type":"Organization","@id":"https:\/\/www.uchealth.org\/today\/#organization","name":"UCHealth","url":"https:\/\/www.uchealth.org\/today\/","logo":{"@type":"ImageObject","inLanguage":"en-US","@id":"https:\/\/www.uchealth.org\/today\/#\/schema\/logo\/image\/","url":"https:\/\/uchealth-wp-uploads.s3.amazonaws.com\/wp-content\/uploads\/sites\/6\/2020\/04\/24135149\/UCHealth-square-logo-1000x1000-1.jpg","contentUrl":"https:\/\/uchealth-wp-uploads.s3.amazonaws.com\/wp-content\/uploads\/sites\/6\/2020\/04\/24135149\/UCHealth-square-logo-1000x1000-1.jpg","width":1000,"height":1000,"caption":"UCHealth"},"image":{"@id":"https:\/\/www.uchealth.org\/today\/#\/schema\/logo\/image\/"},"sameAs":["https:\/\/www.facebook.com\/uchealthorg\/","https:\/\/x.com\/uchealth","https:\/\/www.instagram.com\/uchealth\/","https:\/\/www.linkedin.com\/school\/14839\/","https:\/\/www.pinterest.com\/uchealthorg\/","https:\/\/www.youtube.com\/channel\/UC41SJI79yjZIe96OajzN22g"]},{"@type":"Person","@id":"https:\/\/www.uchealth.org\/today\/#\/schema\/person\/da7733ff5562e48e55c027d111ee5911","name":"Todd Neff, for UCHealth","image":{"@type":"ImageObject","inLanguage":"en-US","@id":"https:\/\/secure.gravatar.com\/avatar\/ba17a8f1358d39c104ff6cb59da7fe21b9bfc792948447c3ac964e93b37aa49f?s=96&d=mm&r=g","url":"https:\/\/secure.gravatar.com\/avatar\/ba17a8f1358d39c104ff6cb59da7fe21b9bfc792948447c3ac964e93b37aa49f?s=96&d=mm&r=g","contentUrl":"https:\/\/secure.gravatar.com\/avatar\/ba17a8f1358d39c104ff6cb59da7fe21b9bfc792948447c3ac964e93b37aa49f?s=96&d=mm&r=g","caption":"Todd Neff, for UCHealth"},"description":"Todd Neff has written hundreds of stories for University of Colorado Hospital and UCHealth. He covered science and the environment for the Daily Camera in Boulder, Colorado, and has taught narrative nonfiction at the University of Colorado, where he was a Ted Scripps Fellowship recipient in Environmental Journalism. He is author of \u201cA Beard Cut Short,\u201d a biography of a remarkable professor; \u201cThe Laser That\u2019s Changing the World,\u201d a history of lidar; and \u201cFrom Jars to the Stars,\u201d a history of Ball Aerospace.","url":"https:\/\/www.uchealth.org\/today\/author\/tneff\/"}]}},"coauthors":[{"id":23,"name":"Todd Neff","link":"https:\/\/www.uchealth.org\/today\/author\/tneff\/"}],"_links":{"self":[{"href":"https:\/\/www.uchealth.org\/today\/wp-json\/wp\/v2\/posts\/63576","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.uchealth.org\/today\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.uchealth.org\/today\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.uchealth.org\/today\/wp-json\/wp\/v2\/users\/23"}],"replies":[{"embeddable":true,"href":"https:\/\/www.uchealth.org\/today\/wp-json\/wp\/v2\/comments?post=63576"}],"version-history":[{"count":10,"href":"https:\/\/www.uchealth.org\/today\/wp-json\/wp\/v2\/posts\/63576\/revisions"}],"predecessor-version":[{"id":80916,"href":"https:\/\/www.uchealth.org\/today\/wp-json\/wp\/v2\/posts\/63576\/revisions\/80916"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.uchealth.org\/today\/wp-json\/wp\/v2\/media\/63580"}],"wp:attachment":[{"href":"https:\/\/www.uchealth.org\/today\/wp-json\/wp\/v2\/media?parent=63576"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.uchealth.org\/today\/wp-json\/wp\/v2\/categories?post=63576"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.uchealth.org\/today\/wp-json\/wp\/v2\/tags?post=63576"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}