Coronavirus disease-2019 , caused by the highly pathogenic virus SARS-CoV-2, demonstrates high morbidity and mortality caused by development of a severe acute respiratory syndrome connected with extensive pulmonary fibrosis (PF). In this Perspective, we argue that adipocytes and adipocyte-like cells, such as pulmonary lipofibroblasts, may play an important role in the pathogenic response to COVID-19. Expression of angiotensin-converting enzyme 2 (ACE2 -the functional receptor for SARS-CoV) -is upregulated in adipocytes of obese and diabetic patients, which turns adipose tissue into a potential target and viral reservoir. This may explain why obesity and diabetes are potential comorbidities for COVID-19 infections. Similar to the recently established adipocyte-myofibroblast transition (AMT), pulmonary lipofibroblasts located in the alveolar interstitium and closely related to classical adipocytes, demonstrate the ability to transdifferentiate into myofibroblasts that play an integral part of PF. This may significantly increase the severity of the local response to COVID-19 in the lung. To reduce the severity and mortality with COVID-19, we propose to probe for the clinical response to thiazolidinediones (TZDs), PPAR agonists, that are the well-known anti-diabetic drugs. TZDs are able to stabilize lipofibroblasts in their "inactive" state, preventing the transition to myofibroblasts and thereby reducing the development of pulmonary fibrosis and stimulating its resolution.

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Dermal white adipose tissue (dWAT) has found little appreciation in the past as a distinct entity from the better recognized subcutaneous white adipose tissue (sWAT). However, recent work has established dWAT as an important contributor to a multitude of processes, including immune response, wound healing and scarring, hair follicle growth and thermoregulation. Unique metabolic contributions are attributed to dWAT as well, at least in part due to thermic insulation properties and its response to cold exposure. Dermal adipocytes can also undergo adipocyte-myofibroblast transition (AMT), a process that is suspected to play an important role in a number of pathophysiological processes within the skin. Here, we discuss emerging concepts regarding dWAT physiology and its significance to a variety of cellular processes.

Obesity and diabetes are established comorbidities for COVID-19. Adipose tissue demonstrates high expression of ACE2 which SARS- CoV-2 exploits to enter host cells. This makes adipose tissue a reservoir for SARS-CoV-2 viruses and thus increases the integral viral load. Acute viral infection results in ACE2 downregulation. This relative deficiency can lead to disturbances in other systems controlled by ACE2, including the renin-angiotensin system. This will be further increased in the case of pre-conditions with already compromised functioning of these systems, such as in patients with obesity and diabetes. Here, we propose that interactions of virally-induced ACE2 deficiency with obesity and/or diabetes leads to a synergistic further impairment of endothelial and gut barrier function. The appearance of bacteria and/or their products in the lungs of obese and diabetic patients promotes interactions between viral and bacterial pathogens, resulting in a more severe lung injury in COVID-19.

Recent advantages in the anatomical understanding of the face have turned the focus toward the subcutaneous and deep facial fat compartments. During facial aging, these fat-filled compartments undergo substantial changes along with other structures in the face. Soft tissue filler and fat grafting are valid methods to fight the signs of facial aging, but little is known about their precise effect on the facial fat. This narrative review summarizes the current knowledge about the facial fat compartments in terms of anatomical location, histologic appearance, immune-histochemical characteristics, cellular interactions, and therapeutic options. Three different types of facial adipose tissue can be identified, which are located either superficially (dermal white adipose tissue) or deep (subcutaneous white adipose tissue): fibrous (perioral locations), structural (major parts of the midface), and deposit (buccal fat pad and deep temporal fat pad). These various fat types differ in the size of the adipocytes and the collagenous composition of their extracellular matrix and thus in their mechanical properties. Minimal invasive (e.g., soft tissue fillers or fat grafting) and surgical interventions aiming to restore the youthful face have to account for the different fat properties in various facial areas. However, little is known about the macro- and microscopic characteristics of the facial fat tissue in different compartments and future studies are needed to reveal new insights to better understand the process of aging and how to fight its signs best.