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As I am preparing this commentary, the second Nor’easter within a week is in its frenzy. (Since that time there have been two more and it’s snowing today!) My longing for summer, enjoying the warm breezes enveloping our shore home in Brigantine, is escalating. Thinking of the beach brings two thoughts to mind – protecting myself from solar radiation (because of my melanoma history) and shedding a few pounds to avoid embarrassment. I was unaware that these were intimately linked.
Adipose tissue is classified as white, brown, and beige. White adipocytes are the most abundant and are mainly involved for storing energy; brown adipocytes, rich in mitochondria, dissipate energy as heat; and beige adipocytes (also called brite adipocytes) fall phenotypically between white and brown adipocytes. (1) Adipose tissue is not just a passive reservoir for energy storage – it is an endocrine organ, secreting hormones known as “adipocytokines” with vast biologic effects affecting metabolism and immunologic status. (2) To date, more than 600 proteins have been identified as being secreted by adipocytes, including leptin (which regulates appetite and energy expenditure – it is inflammatory, atherogenic, and profibrotic), adiponectin (anti-inflammatory, anti-atherogenic, and improves insulin sensitivity), apelin (vasoactive peptide that regulates cardiovascular function and insulin sensitivity), resistin (regulates insulin resistance, inflammation, and cardiac function), FGF 21 (enhances brown fat thermogenesis, improving glucose and lipid metabolism), IL-6 and TNF (inflammatory, atherogenic, and profibrotic), and many others with a panoply of biologic effects. (1).
It has also become clear that aberrant immune function within adipose tissue in obesity, including an accumulation of pro-inflammatory immune cell populations, plays a significant role in the development of systemic, chronic, low-grade inflammation, increasing the possibility of multiorgan dysfunction. Poor metabolic control, insulin resistance, inflammation, and impaired immune function are hallmarks of immunosenescence and obesity. (3)
Adipose tissue from different anatomic locations can display distinct physiological traits. Visceral (retroperitoneal, mesenteric, perirenal, perigonadal) white adipose tissue is associated with metabolic dysfunction, whereas subcutaneous (SC) white adipose may exert protective effects on metabolic function. (1)
UV can penetrate the epidermis and into the mid-dermis, but not into the SC fat tissue of human skin. Kim et al have demonstrated the SC adipose tissue in chronically sun-damaged skin contains less fat than naturally aged skin, and even a single UV exposure of human skin reduced lipid synthesis in the underlying SC fat tissue through transcriptional regulation of lipogenic enzymes (acetyl CoA carboxylase, fatty acid synthase, and stearoyl CoA desaturase), of their transcription activator sterol regulatory element-binding protein-1 (SREBP-1), and two key adipogenic transcription factors, (CCAAT/enhancer-binding protein-alpha and peroxisome proliferator-activated receptor-gamma). (4)
Kim et al studied primary cultured adipocytes that were treated with conditioned medium from UV or sham-irradiated keratinocytes and fibroblasts. Young and older healthy participants provided SC fat from sun-exposed and sun-protected skin. Sun-protected skin from other participants was irradiated with UV. Differentially expressed adipochemokines were screened by cytokine array, and confirmed in vitro and in vivo. Specific adipochemokines were greatly induced in SC fat by UV exposure. They could impair triglyceride synthesis via downregulation of lipogenic enzymes and SREBP-1. Additionally, UV irradiation induced infiltration of adipose tissue macrophages responsible for the secretion of several chemokines into SC fat. The authors concluded that these UV-induced adipochemokines might be implicated in the reduction of lipogenesis in SC fat, leading to impairment of fat homeostasis and associated comorbidities such as obesity. (5)
In the editorial that accompanies Kim et al, Balato and Raimondo suggest that the bridge between UVB irradiation and SC adipose tissue is keratinocytes and fibroblasts that may produce adipochemokines, including C-X-C chemokines such as ENA-78. The concept of bidirectional cross talk between skin and adipose tissue represents a dynamic interplay between the two. (6)
There is increasing data confirming that psoriatic patients treated with systemic biologic agents such as TNF inhibitors exhibit a lower cardiovascular event risk than patients treated with phototherapy. Wu et al have demonstrated that the cumulative exposure to TNF inhibitors is associated with an incremental cardiovascular risk reduction compared to phototherapy. (7) The research by Kim et al demonstrating that ultraviolet light diminishes SC adipose tissue, and its protective effect on the metabolic syndrome, may explain the systemic benefit of biologic agents in reducing the cardiac comorbidity of psoriasis.
The bottom line is that when I’m in Brigantine I should practice strict photoprotection and jog along the beach – I’ll just have to fantasize about snoozing, wining, and dining.
Point to Remember: Ultraviolet light may diminish the protective effects of subcutaneous adipose tissue via adipocytokines.
- Zhu O, Scherer PE. Immunologic and endocrine functions of adipose tissue: Implications for kidney disease. Nat Rev Nephrol 2018; 14: 105-20.
- Froy O, Garaulet M. The circadian clock in white and brown adipose tissue: Mechanistic, endocrine, and clinical aspects. Endocr Rev 2018; Feb 27 [Epub ahead of print].
- Trim W, et al. Parallels in immunometabolic adipose tissue dysfunction with ageing and obesity. Front Immunol 2018; 9: 169.
- Kim EJ, et al. UV modulation of subcutaneous fat metabolism. J Invest Dermatol 2011; 131: 1720-6.
- Kim EJ, et al. Adipochemokines induced by ultraviolet irradiation contribute to impaired fat metabolism in subcutaneous fat cells. Br J Dermatol 2018; 178: 492-501.
- Balato A, Raimondo A. Novel interactions among ultraviolet B, skin, and adipose tissue. Br J Dermatol 2018; 178: 327-8.
- Wu JJ, et al. The risk of cardiovascular events in psoriasis patients treated with tumor necrosis factor-alpha inhibitors. J Am Acad Dermatol 2018; Feb 27 [Epub ahead of print].
*Image from Pixabay
Dermatology Insights and Inquiries (DI&I) is the 2017 Recipient of the AAD Sulzberger Dermatologic Institute and Education Grants Committee’s Program for Innovative Continuing Medical Education in Dermatology (PICMED) Grant. The PICMED project and DI&I are funded by an endowment established by the Skin Disease Education Foundation and the Elsevier Foundation.