Gluttony, sloth and the metabolic syndrome: a roadmap to lipotoxicity.

Source

Department of Internal Medicine, University of Texas Southwestern Medical Center, Touchstone Center for Diabetes Research, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA. Roger.Unger@utsouthwestern.edu

Abstract

Once considered divine retribution for sins, comorbidities of obesity (metabolic syndrome) are today attributed to obesity-induced metabolic defects. Here, we propose that obesity and hyperleptinemia protect lipid-intolerant nonadipose organs against lipotoxic lipid spillover during sustained caloric surplus. Metabolic syndrome is ascribed to lipotoxicity caused by age-related resistance to antilipotoxic protection by leptin.

PUBMED ARTICLE

Ah, what a marvelous article with a fascinating take on metabolic syndrome! Unfortunately it’s laden with scientific/medical jargon and its concepts, which aren’t particularly complicated, are lost in a sea of latin/greek based words. Hopefully I can unpack the paper for you and pepper in a little bit of my thoughts on what the authors have to say. I’ve decided to do this in two parts, since the review article is dense and long, so here is part I!

America’s Favorite Cardinal Sins

Until relatively recently, obesity caused by diet was a relatively rare occurrence that mostly plagued the upper class. In the sixth century AD, the church listed 7 cardinal sins, among them gluttony, or overeating/overnutrition, and sloth, or under-exertion/lazy-couch-potato-ness, and individuals suffering from obesity and its complications (such as metabolic syndrome) were thought to be punished by divine intervention.

Evolution – Built in Kill Switch for the Greedy?

The authors make an argument that perhaps the deadliness of gluttony and sloth is evolutionary in nature, with obesity leading to the activation of specific genes that lead to the elimination/death of individuals who consume a disproportionate amount of energy resources for the good of the rest of society. Their example is the existence of a gene encoding PCSK9, a protein whose only function is to degrade (destroy) low-density lipoprotein receptors, which leads to an increase in LDL-cholesterol in the bloodstream and the clogging of arteries. Clogged arteries lead to heart disease, heart attacks and death. Why else, the authors argue, would we have a gene that turns on during over-eating that hastens us to our graves if not for the evolutionary benefit of humanity? As interesting an idea as this is, I think this might be stretching it, especially since obesity complications don’t typically cause death before people are of child-bearing age, and the entire purpose of Darwin’s “survival of the fittest” is the passing down of genes (ie having kids).

Viva Twinkies and McDonalds? – Lamest/Worst Revolution Ever

Next, the authors lament the ‘gastronomic’ (ie food) revolution with the invention of commercial mass production of “food” (think twinkies and McDonalds), stating that the average American consumes 500cal/day more than they did 50 years ago. 2/3 Americans are overweight/obese and 1/6 have a metabolic disorder, with the numbers on the rise.

‘Merica – Eatchu’ sum!

In order to develop metabolic syndrome, you must overeat all the time (chronic caloric surplus). The development of metabolic syndrome is even faster if the excess calories come from fatty and sugary foods. The US food industry has done a fantastic job of inventing “adipogenic nutrient mixtures” (ie stuff that’ll make you fat) in the form of syrupy-sweet sugar packed drinks and carbohydrate-rich-dripping-with-fat foods (ie Super-sized Double Bacon Cheeseburger with a side of fries and a large coke). These ‘nutrients’ cause the body to start cranking insulin out like crazy (hyperinsulinemia) and increases expression of proteins that cause cholesterol levels to rise (SREBP-1c). To add to this lovely havoc, glucose can be used to make fats from scratch (ie “de novo lipogenesis”), allowing the extra calories (and boy will there be extra calories after THAT meal) to be stored as triacylglycerol.

In addition to creating monstrosities masquerading as foods, the US food industry specifically and aggressively targets children in their marketing campaign because it has been shown that many food preferences are formed during childhood and that these food preferences can endure throughout life. If they can get a child hooked, they’ve got a potential junkie for life.

Luddite Alert – Technology is Turning You Into A Lump

In addition to the technological leaps and bounds of the last century resulting in revolutions in the commercial food sector, technology has also made our lives considerably easier. We have less labor to do – cars, dishwashers, washing machines, driving lawn mowers – and we have an explosion of new entertainment technologies – internet, video games, smartphones, reddit – that allow us to keep our butts firmly planted on a soft cushion. We’ve reduced our work and entertainment from full body movements to fingers flying over keyboards and eyes darting around a screen. Although technology is marvelous, it has enabled us succumb to sloth and reduced our calorie burning. Pair sitting around with convenient fast “food,” and you have a recipe for metabolic disaster.

Read Part II Read Part III