Obesity, diabetes and gastrointestinal cancer are frequently linked to western-style diet, high fat/high sugar diet. However, the molecular mechanisms responsible for this are not fully understood. Researchers have gained some new insights that help to better understand this connection. These findings provide an important basis for the development of non-invasive therapies.
Excess nutrient uptake and altered hormone secretion in the gut contribute to a systemic energy imbalance, which causes obesity and an increased risk of type 2 diabetes and colorectal cancer.
The intestine is essential for maintaining our energy balance and is a master at reacting quickly to changes in nutrition and nutrient balance. It manages to do this with the help of intestinal cells that among other things are specialized in the absorption of food components or the secretion of hormones. In adult humans, the intestinal cells regenerate every five to seven days. The ability to constantly renew and develop all types of intestinal cells from intestinal stem cells is crucial for the natural adaptability of the digestive system. However, a long-term diet high in sugar and fat disrupts this adaptation and can contribute to the development of obesity, type 2 diabetes, and gastrointestinal cancer.
The gut, as the body’s digestive and largest endocrine system, serves as a central regulator of energy and glucose homeostasis and quickly responds to dietary and nutritional changes. Constant overnutrition is thought to lead to intestinal maladaptation and dysfunction and to contribute to the development of obesity and prediabetes. This is evident as two hallmarks of obesity, excessive food intake and a reduced stimulation of postprandial insulin secretion by gut hormones, are linked to impaired gut function. Moreover, differences in gut morphology and physiology have been observed between lean and obese individuals. Intestinal functions are carried out by specialized epithelial cells lining the gut: absorptive enterocytes, antimicrobial-peptide-secreting Paneth cells, hormone-secreting enteroendocrine cells (EECs), mucus-secreting goblet and chemosensory tuft cells. The cells of the intestinal epithelium are constantly generated from intestinal stem cells (ISCs). ISC identity is defined by multi-lineage potential and self-renewal capacity, but also by properties that are not hard-wired, such as the proliferative, epigenetic and metabolic state.
western-style diet to increased risk of disease
The scientists assume that intestinal stem cells play a special role in maladaptation. Using a mouse model, the researchers investigated the effects of a high-sugar and high-fat diet and compared it with a control group.
The researchers found that the small intestine increases greatly in size on the high-calorie diet. They profiled 27,000 intestinal cells from control diet and high fat/high sugar diet-fed mice. Using new machine learning techniques, they thus found that intestinal stem cells divide and differentiate significantly faster in the mice on an unhealthy diet. The researchers hypothesize that this is due to an upregulation of the relevant signaling pathways, which is associated with an acceleration of tumor growth in many cancers. This could be an important link: Diet influences metabolic signaling, which leads to excessive growth of intestinal stem cells and ultimately to an increased risk of gastrointestinal cancer.
With the help of this high-resolution technique, the researchers have also been able to study rare cell types in the intestine, for example, hormone-secreting cells. Among their findings, they were able to show that an unhealthy diet leads to a reduction in serotonin-producing cells in the intestine. This can result in intestinal inertia (typical of diabetes mellitus) or increased appetite. Furthermore, the study showed that the absorbing cells adapt to the high-fat diet, and their functionality increases, thus directly promoting weight gain.
Important of Healthy diet and developing alternative non-invasive therapies
These and other findings from the study lead to a new understanding of disease mechanisms associated with a high-calorie diet. What they have found out is of crucial importance for developing alternative non-invasive therapies. To date, there is no pharmacological approach to prevent, stop or reverse obesity and diabetes. Only bariatric surgery causes permanent weight loss and can even lead to remission of diabetes. However, these surgeries are invasive, non-reversible and costly to the healthcare system.
Karimi, H.
Master of clinical Nutrition & Dietetics
Reference
- Aliluev A, et al. Diet-induced alteration of intestinal stem cell function underlies obesity and prediabetes in mice. Nature Metabolism. 2021.
