Censored Ob*sity, Censured Ob*sity
Problematic associations with polyautoimmunity and Multiple autoimmune syndrome
In many of the studies I’ve reviewed so far, obesity has been noted as a risk factor for autoimmune disease, or has been noted to be associated with various autoimmune diseases. Prior to subscribing to Ragen Chastain’s excellent substack, Weight and Healthcare, I would have left these associations unexamined. This 2018 article from Huffington Post provides an overview of the fat activist position and community. The Weight and Healthcare newsletter reviews and debunks the science of obese and overweight classifications. Chastain works to debunk scientifically unsound interventions by healthcare practitioners, who often have undisclosed connections to the weight loss industry. The interventions she criticizes do not lower weight long term, and often have the opposite result—increasing weight in participants and negatively affecting their health.
I learned that the fat activist community censors the terms “obese” and “overweight” with asterisks in place of “e”s to highlight the measurement’s lack of scientific basis for health or health management. I’m a bigger fan of the term censure—to express formal disapproval—as opposed to censor. I have a knee jerk negativity toward censorship. I think the asterisks can also express censure, and I plan to adopt it going forward as a marker of my skepticism of the ob*sity and overw*ight classifications. What follows is an interrogation of some of the associations and assumptions of the literature I reviewed as part of my exploration of Multiple autoimmune syndrome, as it relates to ob*sity and overw*ight classifications.
Polyautoimmunity in Rheumatoid arthritis & Systemic lupus erythematosus
I reviewed polyautoimmunity (when one person meets the study classification criteria for two or more autoimmune diseases) in Rheumatoid arthritis and Systemic lupus Erythematosus here and here. The studies I reviewed reported that ob*sity is a risk factor for polyautoimmunity in Rheumatoid arthritis and Systemic lupus erythematosus. The Weight and Healthcare newsletter has inspired, and taught me, to interrogate associations like these. Is ob*sity a risk factor for polyautoimmunity or is the opposite true, especially given the scientific consensus that autoimmunity is present considerably prior to patients displaying clinical signs and symptoms that meet disease classification criteria? Sub-clinical, unidentified, or mis-identified, autoimmunity makes it difficult to pinpoint exactly when autoimmune disease started in an individual, and thus difficult to determine whether ob*sity preceded polyautoimmunity, or vice versa. There’s also the confounding factor of the stress of living in a higher weight body in a weight biased society. Does the stress of weight bias, and not a baseline higher weight, contribute to the development of polyautoimmunity? I don’t have answers to these questions, and neither do the researchers who used the scientifically problematic measurement of ob*sity and overw*ight as associated risk factors for polyautoimmunity.
The Leptin Theory & Ob*sity
The Leptin Theory proposes a fascinating and compelling explanation for why women have a higher risk of autoimmune disease compared to men. In my review of The Leptin Theory, I side-stepped the authors’ problematic recommendations for testing The Leptin Theory. I considered them to be outside of the scope of my review, and I wanted to separate these problematic recommendations from the theory itself, which I find quite persuasive. The authors cite one study from 1996 that found that the association of plasma levels of leptin were associated with higher levels of body fat. From this, the authors appear to extrapolate that Body Mass Index (BMI) is an indirect measure of leptin levels, and that studies showing an association between high BMI and autoimmune disease indicate higher leptin levels. This is a thin scientific reach for me. The authors’ study recommendations center on
studying whether there is an increase in Autoimmune thyroid disease that rises in tandem with the increase in ob*sity in the U.S. {I don’t know how researchers would do this, considering the under-diagnosis of autoimmune diseases in this country, an absence of comprehensive research registries, and the problematic scientific foundation of the BMI measurement, and thus the ob*se and overw*ight classifications. The authors also note that disruptions in thyroid function, whether it meets clinical disease criteria or not, can cause weight gain. Any study associating the two would need to rigorously determine which came first.}
as men’s ob*sity rises, there should be a proportional rise in Hashimoto’s thyroiditis in men. {The same problems as in (1) apply here.}
high leptin levels should be found as predictive for the development of Autoimmune thyroid disease. {Yes, this can and should be studied, without the inaccurate and stigmatizing noise of ob*se and overw*ight classifications!}
studying inflammatory differences over time in healthy patients who advance to subclinical hypothyroidism and finally Hashimoto’s thyroiditis {yes!}. Or studying differences in BMI over time in healthy patients who advance to subclinical hypothyroidism and finally Hashimoto’s thyroiditis {no!}.
(Merrill & Mu, 2014)
Leptin’s Status? It’s complicated…And Full of Resistance
Ob*sity is, very unfortunately, fundamentally built into the concept of Leptin—Leptin is regulated by the “Ob*sity gene” (known more commonly as OB). Leptin has a number of complex functions as both a hormone and a pro-inflammatory cytokine (a class of protein that exert either a pro-inflammatory or anti-inflammatory effect on other cells). High circulating levels of leptin in the body affect the hypothalamus, pituitary and thyroid gland (known as the hypothalamus-pituitary-thyroid axis) to give the body signals of fullness and decrease weight. Low circulating levels of leptin in the body are supposed to stimulate hunger signals and increase weight. But…there’s a mixture of evidence and theory that leptin resistance can develop through several different mechanisms
leptin travels from fat tissue, to the circulatory system, to the hypothalamus. To get from the circulatory system (arteries and veins) to the hypothalamus, leptin has to cross the blood-brain barrier (the complex tissue barrier that provides some protection to the brain). The theory, and one study, show that when serum leptin levels are above the standard range (don’t get me started on lab standards and the problematic science behind those), leptin levels do not increase in brain tissue or cerebrospinal fluid. The blood-brain barrier may shut down to further leptin transport at a certain level, disrupting the hypothalamus-pituitary-thyroid regulatory mechanisms and concentrating circulating leptin levels in the rest of the body.
“Leptin concentrations and leptin-related effects are directly dependent upon the transcription of the OBgene; therefore, the factors affecting this can considerably affect the status of adipose tissue and the development of leptin resistance.” Essentially, an OBgene-related decrease in leptin levels in fat cells might lead to an increased volume of fat tissue until the required leptin level is achieved. Serum leptin levels stay at standard levels, even when external body fat is high.
(Gruzdeva et. al, 2019)
Leptin is a rich avenue of exploration for the way that autoimmune diseases develop, but its complex interaction with higher weight bodies is unproven and problematic. And that’s because the associations between leptin and higher weight bodies are based on the scientifically dubious measurement of Body Mass Index and through it, ob*se and overw*ight classifications. As long as the science of Leptin is rooted in BMI, it’s on shifting sands. Luckily, there’s a solution to this, study leptin and autoimmunity, and jettison the BMI-based classifications of “ob*se” and “overw*ight.”
Ob*sity-Related Citations from Reviewed Studies
Versini M, Jeandel PY, Rosenthal E, et al. Obesity in autoimmune diseases: not a passive bystander. Autoimmun Rev. 2014;13:981–1000.
Winer S, Paltser G, Chan Y, et al. Obesity predisposes to TH17 bias. Eur J Immunol. 2009;39:2629–2635.
Arai S, Miyazaki T. Impacts of the apoptosis inhibitor of macrophage (AIM) on obesity-associated inflammatory diseases. Semin Immunopathol. 2014;36:3–12.
Earthman CP, Beckman LM, Masodkar K, et al. The link between obesity and low circulating 25- hydroxyvitamin D concentrations: considerations and implications. Int J Obes (Lond). 2012;36:387– 396.
References
Gruzdeva O, Borodkina D, Uchasova E, Dyleva Y, Barbarash O. Leptin resistance: underlying mechanisms and diagnosis. Diabetes Metab Syndr Obes. 2019 Jan 25;12:191-198. doi: 10.2147/DMSO.S182406. PMID: 30774404; PMCID: PMC6354688.
Merrill SJ, Mu Y. Thyroid autoimmunity as a window to autoimmunity: An explanation for sex differences in the prevalence of thyroid autoimmunity. J Theor Biol. 2015 Jun 21;375:95-100. doi: 10.1016/j.jtbi.2014.12.015. Epub 2015 Jan 6. PMID: 25576242.