Obesity and mild to moderate impaired carbohydrate tolerance develops in the obese phenotype of the LA/Ntul//-cp (corpulent) rat strain by 6 weeks of age. Groups (n=12-20 rats/phenotype] of female congenic lean and obese LA/Ntul//-cp (corpulent) rats were fed ad libitum standardized Purina #5012 diet ad house water for 4, 14, or 24 months of age. Measures of Body weight (BW) and of resting oxygen consumption (RMR; VO2) at thermal neutrality and for up to 45 minutes of (4°C) spontaneous cold exposure, and norepinephrine-stimulated thermogenesis (100 ug. s.c.) were determined at each age. Body weights of lean rats increased only gradually during the study (p=n.s.), but weights of obese phenotype were ~2-fold greater at 4 months (p=<0.05), 14 months (p-<0.01), and ~3.5 to 4-fold greater at 24 months of age (p=<0.01). Resting metabolic rates in the lean phenotype trended to decrease modestly by 24 months (p=<0.05) and were greater than resting metabolic rates in the obese phenotype at all ages studied (p=<0.05). Cold exposure at 4°C resulted in a dramatic ~5-fold increase in the oxygen consumption after 5 minutes in 4-month-old rats, which subsided to ~2x resting metabolic rate within 15 minutes and remained constant thereafter in the lean phenotype. In 14-months old lean rats the increase in oxygen consumption at 5 minutes averaged ~4-fold increase over resting levels and returned to ~2x resting levels from 15 to 45 minutes 4°C exposure. In 24-month-old lean rats however, the cold induced increases in metabolism were markedly diminished to only ~3x resting metabolic rates at 5 minutes cold exposure but remained similar to the other lean age groups thereafter. In the obese phenotype, the peak responses at 5 minutes were lower than those of lean rats at 5 minutes in 4- and 14-month-old rats and were significantly impaired in 24-month-old rats at all times measured. Norepinephrine resulted in a >1.5-fold increase in oxygen consumption in the lean phenotype at all ages studied, while in obese rats norepinephrine resulted in a~1.4-fold increase in oxygen consumption at 4 months of age with non-significant ~1.1 to 1.2-fold increases at the two older ages. In both phenotypes, the resting and the norepinephrine-stimulated oxygen consumption responses tended to decrease with increasing age. The results of this study demonstrate that the body weights of the obese phenotype are significantly greater than their lean littermates throughout the age spectrum studied, and that both resting metabolic rates, 4°C cold, and norepinephrine-stimulated thermogenesis are decreased in the obese compared to the lean phenotype and become further decreased with advancing age

The incidence of overweight, obesity and non-alcoholic fatty liver disease (NAFLD) in Western society have increased to epidemic proportions in the past decade and are now recognized as significant progressive comorbidities contributing to complications of COVID-19. Adiposity reflects an imbalance in energy homeostasis, where cumulative energy intake chronically exceeds net energy expenditure often associated with Insulin resistance (IR) and other endocrinopathies which further impairs parameters of energy balance and expenditure. A primary function of white adipose tissues (WAT) is nutritionally and hormonally mediated lipogenesis and lipid storage in the form of triglycerides, derived from dietary or de novo substrates. Central adiposity, including visceral adipose depots is typically associated with chronic inflammation and endocrine dysregulation including elevations in plasma insulin, amylin, and hyperlipidemia, a suppressed immune response, and elevations in markers of inflammation in peripheral tissues, which are contributory to the progression of the cardiovascular, renal, and other significant comorbid sequela that often follow. Multiple mechanisms are operative in obesity that contribute to the magnitude of severity of COVID-19 illness. 1: The SARS-CoV-1 can infect multiple organ systems that contain ACE2 receptors, including WAT; 2. The SARS-CoV-2 virus contains abundant viral spike proteins compatible with the ACE2 receptors of WAT, enabling the efficient uptake of COVID-19 viral particles; 3: WAT secretes the inflammatory cytokines TNF, IL-6, and others, augmented by adipocytokines leptin and resistin, which together facilitate the creation of an enhanced inflammatory state combined in concert with the suppressed immune state; 4: WAT secretes leptin, TNFα, CXCL-10 and other inflammatory adipokines that are common factors in central obesity have been correlated with the severity of COVID-19 in obese individuals, and 5: the cytokine IL-6 from WAT acts as a primary mediator of the cytokine storm inflammatory response which typically leads to the development of an acute respiratory distress syndrome (ARDS) often with dire consequences in later stages of COVID-19. NAFLD also correlates with hyperlipidemia and the severity of COVID-19 in a similar manner. Thus, the inflammatory markers and the lipogenic characteristics of IR, excess adiposity, chronic inflammation, and related sequelae are significant opportunistic contributors to the magnitude of severity and outcome of the morbidity and mortality observed in COVID-19 illness. The purpose of this editorial review is to present an overview of the contributions of obesity and its endocrinologic and inflammatory pathophysiologic sequelae on COVID-19 illness.

Multiple studies indicate that the thermic responses to diet and cold exposure may be impaired in obese rodents and are likely secondary to the combined contributions of sympathetic and thyroidal components of nonshivering thermogenesis (NST). T4 is normally deiodinated via outer ring deiodinase activity by D‐1 and/or D‐2 deiodinase activity to form hormonaly active T3 during fed and cold environments, or inner ring deiodinase activity via D‐3 to form reverse T3 (rT3) during food or energy deprivation. The effect of 14 hours of 4°C cold exposure on the obese phenotype of the LA/Ntul//‐cp rats was determined in normally reared young female animals 8 to 9 weeks of age and fed the Purina Chow #5012 ad libitum throughout. Body weights and adipose tissue mass were greater in the obese than the lean phenotype (p=<0.05). RMR and the dose related thermic responses to norepinephrine (NE, 200 ug., s.c.) were greater in lean than in obese. Cold exposure at 4°C resulted in decreases in rectal but not core temperature in obese rats, and the thermic responses to 45 minutes of 4°C cold exposure on VO2 were typical but were significantly greater in lean than obese animals at all time points measured. Circulating T4 concentrations were similar in lean and obese rats and serum T3 but not T4 concentrations increased dramatically in both phenotypes following the cold exposure, consistent with phenotype‐ and maximal IBAT‐linked changes in T4‐5’‐deiodinase activity / mg protein in kidney, liver and IBAT and in temperature linked increases in IBAT deiodinase activity / mg tissue protein in this strain. When D‐1 and D‐2 deiodinase activity was computed / tissue mass, further analysis indicated that D‐1 was the predominating deiodinase in liver, kidney, and gastrocnemius muscle, while in IBAT D‐2 > D‐1 activity / IBAT depot and was greater in obese than lean rats. Cold exposure was associated with modest increases in net kidney deiodinase activity only in kidney. Thus, the cold induced increases in circulating T3 in lean and obese rats are likely attributed at least in part to modest increases in renal T4‐5’ D‐2 deiodinase activity, in addition to maximal rates of conversion in other tissues in possible combination with decreases in hormone clearance rates during cold induced stress.

The tradition of Chinese Medicine (TCM) has been in use and development for thousands of years, where it has been applied in some form for the treatment of nearly every common illness. TCM is currently undergoing a resurgence in interest and in providing an adjunct to allopathic medical care virtually worldwide. TCM therapeutics may be administered in many forms from capsules, to powders, homogenates, tinctures and decoctions. Si Wu Tang, a derivative of the traditional Chinese including Formulas, is a combination of substances that may function in a synergistic manner to promote a calming effect and an amelioration of symptoms of hypertension. Such formulas are often used in TCM to treat or alleviate a wide range of the common illness and disorders of both Eastern and Western society. Reported beneficial effects include improvements in circulatory, cardiovascular, mood, endocrine metabolic and reproductive disorders. One such TCM formula commonly recommended is the Wu Cao Si Wu Tang [SWT]formula, used to treat the hypertension of obesity and a variety of other disorders. Hypertension is a key risk factor for cardiovascular morbidity and mortality and is a leading cause of end-stage renal disease; over 7 million US deaths per year may be directly attributed to pathophysiologic complications resulting from poor control of blood pressure. While numerous advances in the diagnosis and treatment of hypertension have had a major impact on decreasing the overall risks and an improved management of this chronic disease, a definitive cure for all causes of hypertension has remained elusive to date. To determine the comparative effectiveness of conventional Western treatment vs. drug free Traditional Oriental Therapy for hypertension, we reviewed the data from independent studies. Wu Cao Si Wu Tang was found to be as effective as allopathic medications in controlling blood pressure in a group of moderately hypertensive patients

Obesity develops in the obese phenotype of the LA/Ntul//‐cp (corpulent) rat strain by 6 weeks of age. Groups [n=12‐20 rats/phenotype] of congenic female lean and obese LA/Ntul//‐cp (corpulent) rats were fed ad libitum standardized Purina #5012 diet for 4, 14, or 24 months of age. Measures of Body weight (BW) and of resting metabolic rate (RMR) at thermal neutrality, and for up to 45 minutes of 4°C spontaneous cold exposure, and norepinephrine‐stimulated (NE) thermogenesis (100 µg sc) were determined at each age. BW of lean rats increased only gradually during the study (p=N.S.), but BW of obese phenotype were 2‐fold greater at 4 months (p=0.05) and increased progressively to 4‐fold greater than lean littermates by 24 months of age (p=<0.01). RMR in the lean phenotype decreased gradually at each age (p=<0.05) and was greater in the lean than the obese phenotype at all ages studied (p=<0.05). Cold exposure resulted in a dramatic 5‐fold increase in the VO2 after 5 minutes in 4‐month‐old rats, which increase in thermogenesis was less dramatic at each successive age. In 24‐month‐old lean rats however, the cold induced increases in RMR were markedly diminished to only ~3x RMR at 5 minutes cold exposure but remained similar to the other lean age groups thereafter. In the obese phenotype, the peak responses at 5 minutes were significantly lower than those of lean rats at 5 minutes in 4‐ and 14‐month‐old rats and were also markedly impaired in 24‐month‐old obese rats. NE resulted in a 1.5‐fold increase in VO2 in the lean phenotype at all ages studied, while in obese rats NE resulted in a ~1.4‐fold increase in VO2 at 4 months with non‐significant 1.2‐fold increases at the two older ages. In both phenotypes, the RMR and the NE‐stimulated VO2 responses tended to decrease with increasing age. The results of this study demonstrate that the body weights of the obese phenotype are significantly greater than their lean littermates throughout the age spectrum studied from 6 weeks of age, and that both resting RMR, cold, and NE‐stimulated thermogenesis are decreased in the obese compared to the lean phenotype, become further decreased with advancing age, and may be a contributing factor in the efficiency of energy conservation and expenditure in the obese phenotype of this animal strain.

Equine herpes virus (EHV‐1) causes wide spread infection among equine populations worldwide. EHV‐1 causes respiratory disease, abortion, neonatal death, paresis, retinopathy and latent viremia. Horses show a transient immunity after natural or experimental EHV‐1 but infection and immune responses to EHV‐1 started to decline after a few months of infection. As a result recovered horses are prone to subsequent EHV‐1 infection. As a result of transient immune responses, effective and lasting vaccination remains a challenge. Human herpesvirus in a murine model provides solid protection to the animals, and re‐infected recovered mice were not easily reinfected after the initial infection. In this study we infected mice with EHV‐1 via intranasal route and after three months mice that had recovered were re‐infected with the same strain of EHV‐1 along with previously placebo control mice that were now infected for the first time in addition to addition of a new new placebo control group. It was proposed that mice that had recovered from a first infection when later challenged with live virus might show some measure of protection, but in fact they showed unexpectedly severe clinical signs. These mice demonstrated severe clinical signs with abdominal breathing, weight loss and a higher mortality rate compared to a same age group of mice who had been exposed to the virus for the first time or the placebo control. The unexpected findings of their worst clinical signs came from postmortem findings and histopathological study, which indicated severe consolidation and profound infiltration of inflammatory cells such that the normal parenchyma and architecture of lungs were completely lost. In this communication Immunopathological findings of the study will be discussed in detail. The results of this study suggest that an immunoreactive mechanism should be considered in designing and selecting epitopes for intranasal vaccine preparation for EHV‐1 and possibly other respiratory infections both in animals and humans. Support or Funding Information Supported by Institutional Resources of the University of Cambridge, UK, the University of Health and Humanities BVI, the Einstein Institute USA, and the University of Science Arts & Technology, Montserrat, BWI.

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White Adipose Tissue (WAT) is typically regarded as a passive storage deposit of excess fat. However, recent research suggests that WAT behaves like an organ system that interacts with the autonomous nervous, endocrinological and immunological systems. Therefore, it is possible that WAT acts as a regulatory organ that keeps the body in homeostasis. This cross-sectional study uses physiological data from 30 patients at the Pinewood Natural Health Centre in Toronto, Canada to derive a description of the role of WAT in the mediation of homeostasis. Statistical methods derive a formula describing the dynamic congruence that contributes to a systems medicine (SM) understanding of the organism. Multiple variables including body parameters, composition, and metabolism, heart rate variability and the immune, autonomous, neural, and endocrinologicial systems were measured and correlated using multiple regression analysis. The null hypothesis was that no variables would correlate; the alternative hypothesis was that at least two variables that would correlate with each other to demonstrate congruence and order. This analysis found strong correlations with parameters of the immune system and metabolism and few correlations with the autonomous nervous system. This suggests that despite the body’s complexity, not all systems may contribute equally strongly to overall homeostasis