High-sugar diets: Discovering human impacts through animal models

Colon sections from control mice (left) and mice fed a high glucose diet for seven days (right). The protective mucus which separates the colon’s epithelial lining (at bottom) from fecal content (above) was thinner in mice given glucose. (UT Southwestern Medical Center)

High-sugar diets can have many negative effects. One way to pinpoint the physical changes they can cause in humans is to test their effects on animal models that share similarities with humans.

Featured articles (these articles have been added to the Science Primary Literature database):

*Alcántar-Fernández, J., González-Maciel, A., Reynoso-Robles, R., Martha Elva Pérez Andrade, de J Hernández-Vázquez, A., Velázquez-Arellano, A., & Miranda-Ríos, J. (2019). High-glucose diets induce mitochondrial dysfunction in caenorhabditis elegans. PLoS One, 14(12), e0226652. [PDF] [Cited by]

Glucose is an important nutrient that dictates the development, fertility and lifespan of all organisms. In humans, a deficit in its homeostatic control might lead to hyperglycemia and the development of obesity and type 2 diabetes, which show a decreased ability to respond to and metabolize glucose. Previously, we have reported that high-glucose diets (HGD) induce alterations in triglyceride content, body size, progeny, and the mRNA accumulation of key regulators of carbohydrate and lipid metabolism, and longevity in Caenorhabditis elegans. Herein, we show that increasing amounts of glucose in the diet induce the swelling of both mitochondria in germ and muscle cells. Additionally, HGD alter the enzymatic activities of the different respiratory complexes in an intricate pattern. Finally, we observed a downregulation of ceramide synthases (hyl-1 and hyl-2) and antioxidant genes (gcs-1 and gst-4), while mitophagy genes (pink-1 and dct-1) were upregulated, probably as part of a mitohormetic mechanism in response to glucose toxicity.”

*Khan, S., Waliullah, S., Godfrey, V., Wadud Khan, M. A., Ramachandran, R. A., Cantarel, B. L., . . . Zaki, H. (2020). Dietary simple sugars alter microbial ecology in the gut and promote colitis in mice. Science Translational Medicine, 12(567), eaay6218. [Cited by]

The higher prevalence of inflammatory bowel disease (IBD) in Western countries points to Western diet as a possible IBD risk factor. High sugar, which is linked to many noncommunicable diseases, is a hallmark of the Western diet, but its role in IBD remains unknown. Here, we studied the effects of simple sugars such as glucose and fructose on colitis pathogenesis in wild-type and Il10−/− mice. Wild-type mice fed 10% glucose in drinking water or high-glucose diet developed severe colitis induced by dextran sulfate sodium. High-glucose–fed Il10−/− mice also developed a worsened colitis compared to glucose-untreated Il10−/− mice. Short-term intake of high glucose or fructose did not trigger inflammatory responses in healthy gut but markedly altered gut microbiota composition. In particular, the abundance of the mucus-degrading bacteria Akkermansia muciniphila and Bacteroides fragilis was increased. Consistently, bacteria-derived mucolytic enzymes were enriched leading to erosion of the colonic mucus layer of sugar-fed wild-type and Il10−/− mice. Sugar-induced exacerbation of colitis was not observed when mice were treated with antibiotics or maintained in a germ-free environment, suggesting that altered microbiota played a critical role in sugar-induced colitis pathogenesis. Furthermore, germ-free mice colonized with microbiota from sugar-treated mice showed increased colitis susceptibility. Together, these data suggest that intake of simple sugars predisposes to colitis and enhances its pathogenesis via modulation of gut microbiota in mice.”

*Seo, Y., Kingsley, S., Walker, G., Mondoux, M. A., & Tissenbaum, H. A. (2018). Metabolic shift from glycogen to trehalose promotes lifespan and healthspan in caenorhabditis elegans. Proceedings of the National Academy of Sciences of the United States of America, 115(12), E2791–E2800. [PDF] [Cited by]

As Western diets continue to include an ever-increasing amount of sugar, there has been a rise in obesity and type 2 diabetes. To avoid metabolic diseases, the body must maintain proper metabolism, even on a high-sugar diet. In both humans and Caenorhabditis elegans, excess sugar (glucose) is stored as glycogen. Here, we find that animals increased stored glycogen as they aged, whereas even young adult animals had increased stored glycogen on a high-sugar diet. Decreasing the amount of glycogen storage by modulating the C. elegans glycogen synthase, gsy-1, a key enzyme in glycogen synthesis, can extend lifespan, prolong healthspan, and limit the detrimental effects of a high-sugar diet. Importantly, limiting glycogen storage leads to a metabolic shift whereby glucose is now stored as trehalose. Two additional means to increase trehalose show similar longevity extension. Increased trehalose is entirely dependent on a functional FOXO transcription factor DAF-16 and autophagy to promote lifespan and healthspan extension. Our results reveal that when glucose is stored as glycogen, it is detrimental, whereas, when stored as trehalose, animals live a longer, healthier life if DAF-16 is functional. Taken together, these results demonstrate that trehalose modulation may be an avenue for combating high-sugar-diet pathology.”

Questions? Please let me know (engelk@grinnell.edu)

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