Obesity is a multifaceted chronic disease whereby changes on a cellular level and overall functioning of the body, can lead to metabolic syndrome, type II diabetes, heart disease, problems with fertility, muscular damage, osteoarthritis, osteoporosis, chronic pain, and psychological problems (anxiety among many others).
Recent models propose that the mechanisms responsible for the development of obesity center around changes in the body’s stem cells. For instance, low-grade systemic inflammation caused by obesity can be harmful to stem cells by changing their ability to grow and regenerate. Other changes in the cellular environment can lead to the premature death of cells and this in turn create a potentially diseased environment for stem cells.
Obesity has lasting effects on gene expression and cellular longevity of stem cells. Recent evidence is suggestive of a bi-directionality of stem cell damage in the “obese environment”, whereby obesity might encourage stem cell dysfunction, and these molecular changes in stem cells as well as the “stem cell niche” in which they occur, might further hasten the development of obesity and associated diseases. It is believed that this transmission can occur through multiple generations.
To illustrate this phenomenon, development in the uterus is a period of rapid growth and tissue transformation, at this stage of a fetus’ life they are vulnerable to any adverse influences which can later in life impact their health. Research suggests that infants that are fatter (have more “fat cells”) and show rapid weight gain after birth are at risk of developing childhood obesity and metabolic syndrome. This is especially in infants born to obese mothers. Genetic predisposition to obesity, shared familial socioeconomic- and behavioral factors, and specific intrauterine effects are supposed mechanisms for these associations.
These results sustain the idea that interventions, specifically during pregnancy, are needed to disrupt the cycle of transgenerational obesity. Further evidence for this hypothesis was provided by researchers that used human umbilical cord-derived mesenchymal stem cells (UC-MSCs) to infuse into obese mice once per week for 6 weeks. They found that UC-MSCs elevated serum interleukin-10 and subsequently promoted macrophage diffusion, leading to the alleviation of insulin resistance. The UC-MSCs helped the Treg cells in the spleen to produce IL-10 which in turn exerted their effect by lowering insulin resistance.
Considering the pathological role of adipose stem cell aging in obesity, focusing on adipogenesis as an anti-obesity treatment, will be a key area of future research, and a strategy to revitalise tissue stem cells that are capable of improving metabolic syndrome.
Various ground-breaking treatments that scientists are proposing for treating obesity have emerged. One of the highlights is potential therapy whereby transplanting human brown-like fat cells, which are human white fat cells that have been genetically modified to become similar to heat-generating brown fat cells, have resulted in the reversal of obesity.
Another novel potential therapy discovered by Scientists at Queen Mary University of London is that by reducing the size of tiny hair-like structures on certain stem cells stops them from turning into fat. The discovery could be used to develop a way of preventing obesity. The researchers showed that during this process of adipogenesis, the length of primary cilia increases was associated with the movement of specific proteins onto the cilia. Furthermore, by genetically restricting this cilia elongation in stem cells the researchers were able to stop the formation of new fat cells.
Obesity is associated with reduced muscle mass and impaired metabolism. Epigenetic changes that affect the formation of new muscle cells may be a contributing factor. According to new research, it seems that in normal versus obese people, different genes were regulated during the maturation process and that methylation changes were significantly more common in subjects who were obese compared to non-obese people.
In obese individuals, the muscle stem cells have been reprogrammed, and this may to some extent explain why muscle cells in obese people have reduced insulin sensitivity and a slower metabolism after they have matured. The question arises; whether the methylations are caused by obesity or do the methylations increase the risk of becoming obese? This serious of events has not been elucidated yet.
Whilst our understanding of the interplay between adipose stem cell aging and adipose hypertrophy is increasing, there is still an unsolved fundamental question: which came first, the chicken or the egg?
References
- Alma, A.; Marconi, G.D.; Rossi, E.; Magnoni, C.; Paganelli, A. Obesity and Wound Healing: Focus on Mesenchymal Stem Cells. Life 2023, 13, 717. https://doi.org/10.3390/life13030717
- Xue J, Gao J, Gu Y, Wang A, Yu S, Li B, Yin Y, Wang J, Su W, Zhang H, Ren W, Gu W, Lv Z, Mu Y, Cheng Y. Human umbilical cord-derived mesenchymal stem cells alleviate insulin resistance in diet-induced obese mice via an interaction with splenocytes. Stem Cell Res Ther. 2022 Mar 21;13(1):109. doi: 10.1186/s13287-022-02791-6. PMID: 35313972; PMCID: PMC8935757.
