Here we go, to BAT, again!
Graphic 1, from Wikipedia: BAT cells have many active mitochondria and WAT cells have hardly any. On the other hand, white fat cells swell, with a huge globule of fatty acids and oils, while BAT does not store fats.
A few WAT (white adipose tissue) progenitor (stem) cells can convert to “Beige adipocytes” in cold-weather conditions, or when stimulated by continuous administration of Triiodothyronine (T3), but they are less efficient heat producers than the BAT is.
White, brown and beige adipocytes (from Wikipedia).
A report from “Medscape”, written by Courtney Southwick, dated 10/17/23, advises us that that the sympathetic-nerve pathways that activate brown fat have been precisely mapped. She credits Prof. Preethi Srikanthan, MD, endocrinologist, and a group at UCLA and other sites, who dissected 8 human cadavers, tracing the sympathetic nerve branches which accompany the 3rd and 4th Cervical (neck) nerves, to the brown fat above and behind the clavicles.
Congratulations, to Shumpei Mori, et al.
The original article, entitled “Sympathetic Innovation of the Supraclavicular Brown Adipose Tissue: A Detailed Anatomical Study”, was Published on October 4, 2023, in “Plos One” (https://doi.org/10.1371/journal.pone.0290455), by Shumpei Mori, Ryan S. Beyer, Breno Bernardes de Souza, Julie M. Sorg, Donald B. Hoover, Harold S. Sacks, Michael C. Fishbein, Grace Chang, Warwick J. Peacock, Maie A. St. John, James Law, Micheal E. Symonds, Olujimi A. Ajijola, Kalyanam Shivkumar, and Preethi Srikanthan,
This unbelievably complicated work, carefully designed, meticulously performed and beautifully presented, is a tour-de-force of anatomical dissection, careful documentation and detailed description. Those with an interest in anatomy and the study of anatomy would do well to view it, at the “DOI” link above.
The authors aver that the “final clinical goal” is “selective regulation of (BAT) activity either using chemical, mechanical, electrical, or thermal therapeutic approaches to control metabolic disorders” (I would suggest that the “final clinical goal” should be prevention of diseases such as obesity; but more on that later).
Ms. Southwick, et al. observe, in their report, that “GLP–1 agonists appear to increase BAT activity” and they suggest that perhaps the new diabetes drugs, Semaglutide (Wegovy, Ozempic) and Tirzepatide (Mounjaro), or perhaps electrical stimulation, could be used to stimulate the brown fat as a treatment for obesity. This idea has already occurred to professor Srikanthan, who is quoted in “Genetic Engineering and Biotechnology News” as saying “While we are lucky to have effective drugs such as Wegovy and Mounjaro, people need to take them long-term for weight loss”.
Ms. Southwick feels that stimulating the BAT would produce only a small effect on obesity, because “[brown fat] deposits, while highly metabolically active, are quite small”, but she must not have been thinking “long-term” (think about the small, yearly cost-of-living increase).
COMMENT
I have nothing but praise for the efforts of Mori et al., in elucidating the sympathetic nervous control of our brown fat. However neither their excellent article, nor any of the twelve reports on it which have appeared in Google already, mentions that BAT may be present in many other areas, as seen in the graphic below.
“Distribution of BAT”, by Sampath SC, Sampath SC, Bredella MA, Cypess AM, Torriani M.
Imaging of Brown Adipose Tissue: State of the Art. Radiology. 2016 Jul;280(1):4-19.
doi: 10.1148/radiol.2016150390. PMID: 27322970; PMCID: PMC4942993.
As seen in these PET scans,, the wide distribution of BAT, in the Interscapular, supraclavicular and axillary regions, the hilum of the lungs, above the kidneys, around blood vessels like the aorta and along the vertebral column) renders the idea of electrical stimulation of BAT difficult to consider.
Further, none of the papers which appear in a cursory search via Google, makes mention of the fact that BAT activation requires the thyroid hormone, T3, as well as sympathetic nerve stimulation.
MY OPINION
(1) It seems futile to propose prescribing drugs like Semaglutide and Tirzepatide, to produce an effect which is automatically achieved by an adequate supply of Thyroid 3.
(2) Almost all obese persons have low T3 syndrome. It would be better to investigate the T3 and reverse T3, calculate the T3/are T3 ratio, detect the low T3 syndrome (intracellular hypothyroidism), if present. Those diagnosed with IH could then be treated with slow-release triiodothyronine? *
Drugs found to be helpful in encouraging weight-loss could then be applied, to treat those who remain obese in spite of normalization of thyroid hormone function.
(3) In my (approximately) 200 cases of IH, no serious side effects of slow-release T3 were encountered. Relief of low T3 syndrome symptoms was universal and a slow return to normal-range BMI was observed.
(4) Therefore, as previously said: all persons with serious, or chronic, medical conditions should have their T3/rT3 ratio calculated and “SR” Triiodothyronine should be prescribed for those diagnosed with IH, prior to considering other diagnoses and their treatment.
(4) Obesity could be avoided in the first place, by application of the principles outlined in “preventive care, as it could be” (click on the link below): subjects tending towards obesity, due to stress-related intracellular hypothyroidism should be diagnosed at the onset of the disease, at which point obesity is preventable.
* Nota bene: in my practice, Triiodothyronine was prescribed only if IH was diagnosed via the T3/rT3 ratio, not as a “knee-jerk” weight-loss modality. I prescribed T4, not Triiodothyronine, for true, uncomplicated hypothyroidism.
FURTHER READING
(1) Please see “Brown Adipose Tissue: Activation and Metabolism in Humans”, by Imane Hachemi1 , Mueez U-Din1,2 , Published online: March 27, 2023, in “Endocrinology and Metabolism”, 2023;38(2):214-222. DOI: https://doi.org/10.3803/EnM.2023.1659
(2) Please also see “brown fat and obesity” (a previous post), at https://gervaisharry.substack.com/p/brown-fat-and-obesity?utm_source=profile&utm_medium=reader2
