Adipose tissue association with inflammation, and the development of insulin resistance

The authors in the review paper assigned this week, “Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes” (1) summarize data that implicate an immune mechanism as a possible cause of insulin resistance and type 2 diabetes in obese individuals. A concluding remark suggests that should further research confirm that diabetes is an inflammatory disease that anti-inflammatory therapies could have a role in prevention and treatment. Of note, immune modulating therapies and monoclonal antibodies are a major focus of new research (2).

Interestingly, for this course in nutritional measurement, the paper notes that WBC, fibrinogen, CRP are all elevated obese diabetic patients. All of these are easily and inexpensive to measure and may be useful from a nutritional viewpoint in identifying patients at risk for progressive chronic conditions.

Insulin resistance seems to be linked to inflammation by the finding that TNF alpha is increased in tissues targeted by insulin hormone (adipose, liver, muscles). Other immune factors and monocyte infiltration are also noted in these tissues in obese individuals. This review provides a window into an association between obesity, insulin resistance/diabetes, and inflammation.

Obviously, the obesity-diabetes-inflammation link is a complex one, and the assigned article, “Fat – An Evolving Issue” shows this complexity just in obesity alone (3). “Three controversial suggestions” are described as factors in obesity – “gut microbiome, stress and endocrine-disrupting chemicals”. Although these factors seem to be downplayed, I suspect these are more of an influence in obesity than they are given credit for in this article. I found it very encouraging to find an article, by a geneticist(!) in 2011 which in its first sentence said to my amazement that “One of the most unexpected and fertile advances in biology engendered through mouse genetics has been the rediscovery that physiology has to be studied ultimately at the level of the entire organism.” (4, my emphasis) The research described shows how Serotonin in the gut plays a major role in inhibiting bone formation. Interestingly one of the other assigned articles on sarcopenia deals with this topic of “bone loss” (5).

I am very interested in the implications of Hans Selye’s stress paradigm and new findings in stress research. For instance, Serotonin has been found to have widespread impact on an organism, whether on the gastrointestinal tract, the platelets, the immune system, or the brain. Although there a many interesting articles on stress, as related to diabetes, serotonin, and inflammation, I found this article particularly relevant, “Serotonin as a New Therapeutic Target for Diabetes Mellitus and Obesity” (6): “In peripheral tissues, suppressing 5-HT signaling might represent a new target for anti-obesity treatment by increasing energy expenditure and improving insulin resistance”.  In nutritional interventions, perhaps there is a link between stress and foods that “irritate” the GI tract (causing endotoxemia (7)) prompting the release of serotonin leading to insulin resistance and diabetes.

(1)    Esser, Nathalie, Sylvie Legrand-Poels, Jacques Piette, André J. Scheen, and Nicolas Paquot. “Inflammation as a Link between Obesity, Metabolic Syndrome and Type 2 Diabetes.” Diabetes Research and Clinical Practice 105, no. 2 (August 2014): 141–50. https://doi.org/10.1016/j.diabres.2014.04.006.

(2)    https://labiotech.eu/top-5-immunotherapies-synteracthcr/

(3)    Speakman, John R., and Stephen O’Rahilly. “Fat: An Evolving Issue.” Disease Models & Mechanisms 5, no. 5 (September 2012): 569–73. https://doi.org/10.1242/dmm.010553.

(4)    Karsenty, Gerard, and Michael D. Gershon. “The Importance of the Gastrointestinal Tract in the Control of Bone Mass Accrual.” Gastroenterology 141, no. 2 (August 2011): 439–42. https://doi.org/10.1053/j.gastro.2011.06.011.

(5)    Budui, Simona L., Andrea P. Rossi, and Mauro Zamboni. “The Pathogenetic Bases of Sarcopenia.” Clinical Cases in Mineral and Bone Metabolism: The Official Journal of the Italian Society of Osteoporosis, Mineral Metabolism, and Skeletal Diseases 12, no. 1 (April 2015): 22–26. https://doi.org/10.11138/ccmbm/2015.12.1.022.

(6)    Oh, Chang-Myung, Sangkyu Park, and Hail Kim. “Serotonin as a New Therapeutic Target for Diabetes Mellitus and Obesity.” Diabetes & Metabolism Journal 40, no. 2 (2016): 89. https://doi.org/10.4093/dmj.2016.40.2.89.

(7)    Pomytkin, Igor A., Brandon H. Cline, Daniel C. Anthony, Harry W. Steinbusch, Klaus-Peter Lesch, and Tatyana Strekalova. “Endotoxaemia Resulting from Decreased Serotonin Tranporter (5-HTT) Function: A Reciprocal Risk Factor for Depression and Insulin Resistance?” Behavioural Brain Research 276 (January 2015): 111–17. https://doi.org/10.1016/j.bbr.2014.04.049.