Brown adipose tissue contributes to adaptive changes in metabolic energy expenditure in response to alterations in diet and environmental conditions, thereby assisting an animal to maintain thermoregulation and energy balance in various mammalian species including man and animals. Cafeteria overfeeding of normally lean rats during early postweaning growth typically results in significant hyperplasia and in an increased capacity non-shivering thermogenesis and energy expenditure in brown adipose tissue (BAT). The Interscapular BAT depot is readily surgically accessible and normally represents approximately one third of the total BAT mass in lean Sprague Dawley (SD) rats. The effects of experimental overnutrition via offering a Cafeteria feeding regimen (Café) combined with surgical reduction of the IBAT mass of adipose tissue cellularity and regional fat deposition was determined in lean SD rats during 8 weeks of postweaning growth and development to adulthood. Groups (n= 8 rats/group) of male, SD rats were fed a Purina Chow diet or the Chow diet plus the Café regimen for 52 days from weaning. An additional group of the Chow+Café regimen were subjected to surgical removal of their IBAT at 4 weeks of age and continued on the Chow+Café thereafter (Café-IBAT). At 80 days of age, measures of adiposity including anthropometrics and the mass and adipocyte cellularity in principle abdominal and subcutaneous fat depots were determined. Body weight (BW) and mid-abdominal girth were ~20% greater in Café and Café-IBAT, while linear growth was similar in all groups. The mass of all fat depots was greater in Café fed animals (p=<0.05) and increased further in subcutaneous depots and total WAT accumulation in the Café IBAT animals (p=<0.05). Adipocyte lipid content and cell diameter of Café > controls in all depots with further increases in abdominal depots with Café-IBAT. Adipocyte number per WAT depots of Café > Control in all depots, with further increases in the Inguinal SC depot. Thus, these results are consistent with regional differences in the effects of Café feeding on postweaning adipose tissue hyperplasia, hypertrophy and depot mass and which underwent additional depot-specific differentiation in Café-IBAT. In conclusion, Café resulted in adipocyte hypertrophy in all depots studied, but the partial reduction of BAT mass in Cafe-IBAT rats resulted in only modest additional impact on overall adiposity during overfeeding, with the greatest impact in the ING SC depot, and thereby consistent with potential thermogenic compensation in other BAT depots to partially minimize the overall impact of the Café overfeeding regimen on developing adiposity in this strain.

Thyroid hormones are known to play a critical role in metabolic adaptation to chronic changes in diet and environment. The prohormone tetraiodothyronine (T4) is converted to the active form, triiodothyronine (T3) in peripheral tissues via actions of outer ring deiodination by D-I or D-II isoforms of T4-5’ deiodinase activity. In contrast, T4 may also become inactivated during periods of caloric depravation via an inner tyrosyl ring D-III deiodinase to form an inactive hormone, 3’5’3 triiodothyronine, or ‘reverse T3’ (rT3). Measures of D-I and D-II were determined in selected tissues obtained from congenic adolescent lean and obese female LA/Ntul//-cp rats when 16 weeks of age following laboratory temperature exposure of 22°C or 14 hours acute cold exposure at 4°C. 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 tissue-linked changes in outer ring T4-5’-deiodinase activity / mg tissue protein and per depot. In Gastrocnemius muscle, only D-II was detected, and gastrocnemius D-II activity of obese increased modestly following cold exposure. In Liver, Kidney, and IBAT and in cold-induced temperature exposure linked increases in IBAT deiodinase activity / mg tissue protein in this strain, but when D-I and D-II deiodinase activity were computed / tissue mass however further analysis indicated that D-I was the predominating adaptive deiodinase in liver, kidney, and gastrocnemius muscle, while in IBAT D-II > D-I activity / IBAT depot and was greater in obese than lean rats. Cold exposure was associated with modest increases in net deiodinase activity only in kidney. Thus, the cold induced increases in circulating T3 in lean and obese rats following cold exposure are likely attributed at least in part to modest increases in IBAT outer ring T4-5’ D-II and renal D-I deiodinase activity, in addition to likely attaining maximal rates of conversion in other peripheral tissues in addition to possible combination with decreases in hormone clearance rates and enhanced receptor occupancy during cold induced stress, and where they contribute to protective measures during dietary or environmental stress.

Atherogenic plasma lipid and glycemic profiles are a common observation in obesity and adult-onset diabetes (T2DM) and may become improved following therapeutic intervention. The effects of the luminal α-glucosidase inhibitor miglitol (MIG) on carbohydrate (CHO) digestion on plasma lipid profiles were determined in groups of adult male obese SHR/Ntul//-cp rats, a genetic model that develops early-onset obesity+T2DM independently of diet. Rats were fed a USDA-formulated, complete diet containing 54% sucrose as the CHO component (Control) or the same diet containing MIG at 150 mg/kg diet admixture ad libitum for < 8 weeks. MIG resulted in a ~15% decrease in energy intake (p = < 0.05), net weight gain (p = < 0.05), and 14% decrease in adiposity (p= < 0.05), in addition to significant (p = < 0.05) decreases in fasting glucose, insulin, glycated hemoglobin, a 20% reduction in glucose area under the curve (AUC; p = < 0.05) a 15% reduction in triglycerides, p = < 0.05) and a 20% reduction in total cholesterol, α- (LDL) and β-lipoprotein (HDL) fractions (p = < 0.05, all comparisons) after the MIG regimen. Liver glucokinase, malic enzyme and glucose-6-phosphate dehydrogenase were also decreased following the MIG regimen (p = < 0.05). In conclusion, these results indicate that therapeutic αglucosidase inhibition via MIG resulted in improvements in multiple insulin-linked atherogenic parameters and may be a useful adjunct in the long-term clinical management of plasma lipid and glycemic profiles in the glucose intolerant states of obesity and T2DM.

Premature dysregulation of gastric emptying in concert with hyperinsulinemia are a common observation in early stages of Type 2 Diabetes (T2DM) and contributes to the magnitude of the typical glycemic excursions and insulinogenic responses following carbohydrate-laden meals. In contrast, in later stages of the disorder gastroparesis may occur secondary to diabetic neuropathy. While dietary measures are often a first line approach,inhibitors of luminal starch digestion have been demonstrated to slow the rate of α-glucosidase and sucrase activity following a carbohydrate mealin man and animals, thereby attenuating the immediate glycemic and insulinogenic responses. The improved glycemic and insulinogenic responses if maintained over the course of weeks or months result in improvements in glycated hemoglobin, insulin sensitivityandglucose disposal in peripheral tissues, with secondary improvements in lipogenesis, plasma lipid profiles including plasma triglycerides and LDL cholesterol fractions. Thus, incorporation of inhibitors of α-glucosidase and sucrase activity posit to become useful adjuncts as monotherapy or in combination with other therapeutic agents including GLP-1 incretin mimetics, phototherapeutics, phyto therapeuticsand other obesity and diabetic therapeutic agents in the clinical management of hyperinsulinemia, obesity, prediabetes, T2DM and insulin resistant states as they occur in man and animals.

Thyroid hormones are well established entities that readily mediate numerous essential biochemically-mediated elements of normal development, growth and energy metabolism (EM) expressed at the genomic level in response to alterations in diet and environment. A family of three highly specific Iodothyronine deiodinases consist of a subfamily of three deiodinase enzymes that exert important roles in the activation and deactivation of thyroid hormones in virtually all somatic tissues of vertebrate organisms. Thus, thyroid hormones can directly bring about genomic-mediated variations in gene expression and in the rate of metabolism including pathways of energy expenditure and in the conservation of energy utilization in peripheral tissues. Groups of lean and obese animals were subjected to measures of resting and norepinephrine stimulated VO2, measures of plasma insulin and glycemic parameters, tissue T3 and total in vitro deiodinase activity in multiple tissues, T4 half-life, and T3 nuclear hepatic receptor binding occupancy. The VO2 of resting and dose related NE stimulated VO2 of lean > obese, and serum and tissue T3 of lean > obese, and T4-5’ deiodinase activity of lean > obese in liver and obese > lean in IBAT. T3 receptor occupancy was decreased and T4 half-life was prolonged in the obese phenotype. These results indicate that net T4 activation to T3 and hepatic T3 nuclear receptor binding is decreased in the obese phenotype, and despite the increase in IBAT mass, the decreases in thyroidal actions and hyperinsulinemia are likely contributors to the decreased capacity for resting and NE-stimulated thermogenesis and contributors to greater adiposity in the obese phenotype of this strain.

To determine the effects of aging, early onset obesity, and genetic predisposition on the progression of glycemic parameters, groups of congenic male lean, obese, and obese-diabetic rats (n= 5-6 rats/group) that share the same genetic trait for obesity (the -cp trait) were reared under normal laboratory conditions and feed Purina Rodent chow ad libitum throughout. Rats were subjected to measures of fasting glucose, insulin, and amylin and glycated hemoglobin and on the glycemic response to an oral glucose tolerance at 4 and 12 months of age. Obese animals weighed more than their lean littermates. Fasting plasma glucose, insulin, and amylin concentrations of obese > lean, in increased further in T2DM-prone animals, with the greatest increases in the oldest animals.

Changes in thyroidal activity occur in aging, where they typically exhibit a U-shaped curve for plasma TSH concentrations, with variable responses in other parameters of thyroidal function and peripheral physiological actions and their pathophysiologic sequelae. The LA/Ntul//-cp rat strain, developed from a cross between a Koletsky Rat and an NIH longevity-prone LA/N strain of unknown origin exhibits one of the longest life spans of the various rodent strains that express a trait for early onset obesity in association with impairments in sympathetic and thyroidal components of non-shivering thermogenesis, insulin resistance and energy metabolism. To determine the effects of aging and obesity from adolescence through much of the projected lifespan of the obese phenotype, groups of congenic lean and obese female LA/Ntul//-cp rats were studied from 4 until 24 months of age. Measures of Resting Metabolic rates (RMR), fasting plasma insulin and glucose, T3, T4, plasma half-life of T4, and computation of T4/T3 ratios were determined as an indication of the capacity for deiodination of T4 to T3 in peripheral tissues and its cumulative effects on RMR. Body weight of obese >>> lean at all ages studied. Plasma Insulin was significantly elevated in the obese phenotype, and decreased with advancing age, while plasma glucose remained within the normal fasting range in all rats of both phenotypes. RMR of lean > obese at all ages studied and decreased with advancing age in both phenotypes. Liver T4-5’ deiodinase activity of lean > obese at all ages studied. Plasma T4/T3 ratios decreased with aging in both phenotypes, with the greatest decrease in the obese phenotype. The T1/2 of 131I-T4 was over 40 % longer in the obese phenotype littermates at 4 months of age (p=< 0.01).These results suggest that conversion of T4 to T3 in peripheral tissues in association with attenuation of hyperinsulinemia contributes to decreases in RMR with aging and is further decreased in the obese phenotype, thereby decreasing the quantifiable availability of tissue T3 mass for thyroidal actions at the genomic level, including decreases in harmful reactive oxygen species (ROS) and other entities as products of intermediary metabolism. Thus, the progressive decreases in plasma insulin and deiodination-mediated activation of T4 may represent a longevity attribute via decreases in resting metabolic rates, and in an associated attenuation of free radical generation and other metabolic factors of aging and longevity in this strain.

Elevations in plasma lipid profiles are a common observation in overweight, obese, hyperinsulinemic, and adult-onset diabetes. The effects of luminal inhibition of starch digestion on parameters of weight gain and plasma lipid profiles were determined in groups of adult obese male T2DM SHR/Ntul//-cp rats. Animals were fed a USDA-formulated, nutritionally complete diet containing 54% sucrose (SUC, CHO) component (Control) or the same diet containing a pharmacologic α-glucosidase inhibitor (1,5 dideoxy-1,5-[(2-hydroxyethyl) imino]-D glucitol; generic miglitol), 150 mg/kg diet, ad libitum for up to 8 weeks. Miglitol resulted in modest decreases in food intake and net weight gain. At the end of the study. heparinized bloods were collected for determination of plasma cholesterol, low-density lipoprotein (LDL) and high density lipoprotein (HDL) fractions. The miglitol-associated luminal inhibition of glucosidase activity resulted in 20% reduction in total cholesterol, and in both α- (LDL) and β-lipoprotein (HDL) fractions. These results indicate that simple inhibition of luminal α-glucosidase activity via miglitol may be a useful adjunct in the clinical management of hypercholesterolemia in states of obesity, T2DM and other glucose intolerant states, in addition to therapeutic applications in enhancing and improving glycemic control in man and animals.

Search for a suitable an animal model may prove to be more productive to determine if insulin resistance and its direct metabolic sequelae might be significant co-contributors to the neuronal declines that occur in NIDDM, obesity, and progression of dementia conditions. The burgeoning prevalence of obesity and overweight conditions from the age of adolescence and throughout the lifespan has reached epidemic proportions in industrialized nations throughout the globe. One of the most prevalent findings in obesity is the emergence of insulin resistance, which is linked to both a persistent inflammatory state and systemic hypoxia in adipose tissue. Insulin resistance impacts several aspects of substrate oxidation and oxidative free radical production in brain and somatic tissues, and it is likely that adipose tissue depots are the source of cytokine-linked chronic inflammation. In studies with aging congenic lean and obese rats chronic hyperinsulinemia and brain shrinkage has now been reported, albeit it in the absence of Type 2 diabetes (NIDDM), hypertension (HTN) or other comorbidities, thereby suggesting that aspects of disordered substrate metabolism including insulin resistance as commonly observed in obesity may be a key contributory factor in the development of a neuroinflammatory linked brain shrinkage with accompanying decreases in brain mass, protein and DNA content, and which were further compromised when fed an isocaloric high vs. a low glycemic insulinogenic diet containing sucrose vs. cornstarch respectively. These findings imply that in this strain of obese rats, chronic insulin resistance due to obesity, which is at least partially caused by dietary variables, is a plausible independent risk factor in the development of neuroinflammation, DNA damage, brain shrinkage, and neural senescence.

To determine the effects of aging and the obese phenotype on Triiodothyronine (T3) generation and thyroidal status, groups of congenic lean and obese female littermate LA/Ntul//-cp rats were maintained on Purina stock diet and house water from 4 until 24 months of age. Body weight and adiposity of obese >>> lean at all post weaning ages studied. Measures of resting oxygen consumption (RMR, VO2) at thermal neutrality (30°C), serum T3, T4, T4:T3 and T3:T4 ratios, tissue T3 concentrations, and T4-5’ deiodinase activity in liver, interscapular brown adipose tissue (IBAT), and gastrocnemius muscle (GNM) were determined at each age group. Measures of RMR were greater in lean than obese at each age (p=<0.05) and declined with age in both phenotypes with the most substantial decrease in the obese phenotype. Measures of serum T4 were greater at age 4 months than at both older ages measured in both phenotypes and remained similar thereafter. Serum T3 tended to increase modestly in each age in both phenotypes. Serum T4:T3 ratios decreased with age while serum T3:T4 ratios increased with age in both phenotypes. Measures of tissue T4-5’ Type II deiodinase activity were determined in isolated homogenates of liver, IBAT and GNM. Tissue activity levels of outer ring T4-5’ deiodinase activity of liver and IBAT showed both phenotype and age effects and decreased with age in both tissues. (Lean > obese; young > older) in both lean and obese phenotypes. GNM deiodinase activity increased only modestly with age in lean but not in obese rats. Liver T3 receptor affinity has also been reported to be decreased in the obese phenotype at 4 months of age. These observations are consistent with impaired sirtuin-mediated and age-associated thyroidal actions in the lean and obese phenotypes and which impairments may be contributory to further age associated decreases metabolic rates observed in the obese phenotype.

The per capita intake of fructose mostly in the form of high fructose corn syrup has increased 4- to 5-fold in recent decades. To determine the impact of dietary fructose on parameters of lipid metabolism in brown adipose tissue in T2DM rats, groups of lean and obese-T2DM rats were fed a nutritionally adequate diet consisting of 54% carbohydrate as either cooked cornstarch (CS) or equal parts CS and fructose (CSF diet) from one until 9 months of age. Measures of initial and final body weight s were recorded. At 9 months of age, measures of interscapular brown adipose tissue mass, and size, number, lipoprotein lipase activity, and lipid content determined. Data were analyzed by ANOVA. The body weights of lean and obese littermates were similar at 4 weeks of age, but the net weight gain of the obese phenotype over the 8 months of observation was twice that of their lean littermates, (p = < 0.01). The IBAT mass of obese rats >> than their lean littermates and was not affected by diet in either phenotype. The IBAT number / depot and lipid content / cell and percent lipid / IBAT depot was greater in obese than lean and was not affected by diet. The IBAT LPL activity of obese >> lean and was greater with the CSF than the CS diet in both phenotypes. In conclusion, these results indicate that the obese phenotype results in marked increases in IBAT mass and cellularity independently of diet. LPL activity of lean >> obese and was increased modestly in both phenotypes with the CSF diet. Thus, long term consumption of an isoenergetic diet high in fructose modulates LPL activity and lipid accumulation in brown adipose tissue in a rodent model of insulin resistance and NIDDM. In addition, the expression of obesity in the obese phenotype is more likely a result of the epigenetic metabolic determinants of obesity rather than the specific type of the dietary carbohydrate consumed per se.

The island nation of Haiti had been Cholera free for over a century prior to the 2010 earthquake which left over 1 million inhabitants homeless, when a key community water source became inadvertently contaminated with the causative organism, V. cholerae (El Toro strain 01) soon after the earthquake. The infectious organism was apparently transmitted via well intentioned Nepalese aid workers visiting the Island. During the 2010-2018 outbreak, over 819,000 people were treated for cholera, resulting in nearly 10,000 deaths. With assistance from the CDC, the U.S. Agency for International Development, and implementing partners including the Pan American Health Organization to further expand epidemiologic and public health initiatives, Haiti was once again declared cholera free in February 2022, having no new cases for over 3 years; however, by Sept 2022 new cases were once again reported, ultimately affecting over 20,000 additional mostly Haitian residents, geographically centered around the Port au Prince area, and in 285 additional deaths from the second wave of the Cholera epidemic. This was followed by over 1150 additional deaths by mid-December 2023 and the designation as a Grade 3 Emergency Hazard Status by the WHO. Because of the high potential for asymptomatic carriers of cholera to develop following a widespread epidemic, additional public health strategies must be vigorously employed including widespread immunization to control and minimize the continued impact of the endemic on community, regional and global wellbeing and hopefully prevent the next epidemic from occurring in Haiti or from spreading to surrounding islands and distant jurisdictions.

Glucocorticoid ablation following adrenalectomy resulted in restoration of the impaired non-shivering thermogenesis and impaired glucose tolerance and insulin resistance in obese LA/Ntul//-cp rats. This is a congenic rat strain where the only difference between the lean and obese phenotypes was the presence of the epigenetic expression of obesity in an NIDDM-free animal model. Groups of young adult obese animals were adrenalectomized, followed by thermogenesis and glycemic assessment thereafter. In an additional subgroup, animals were administered insulin daily in an attempt to maintain the insulin resistance state. Adrenalectomy resulted in a complete restoration of normal resting and norepinephrine stimulated thermogenesis and an amelioration of the glycemic parameters of insulin resistance.

The burgeoning prevalence of obesity and overweight conditions including NIDDM and dysregulation of energy balance are rapidly approaching epidemic proportions in much of Western society and imposing a significant burden on available health care resources. Once diagnosed, treatment is typically a life-long effort to attenuate the continued progression of pathophysiologic sequela of the disorders. Since the predominate proportion of macronutrient energy source in most Western diets is often carbohydrate, typically more than 50% by weight at ~4 kcals/gram, efforts to modulate the impact of dietary CHO on parameters of adiposity and weight gain were investigated. This study determined the effects of delayed carbohydrate digestion on energy intake and consequent weight gain groups of young adult, obese-NIDDM rats that were fed a USDA-formulated, hyperinsulinemic diet consisting of 54% sucrose plus essential fats, proteins, micronutrients and fiber for up to 8 weeks, or the same diet containing 150 mg/kg of (1,5 dideoxy-1,5-[(2-hydroxyethyl) imino]-D glucitol; generic miglitol). Measures of daily energy intake and weight gain were determined at weekly intervals. Adiposity was determined by dissecting major fat depots at the end of the study and determining adipose tissue mass and cellularity. Miglitol resulted in 20% less energy intake and weight gain, and corresponding decreases in adiposity after 8 weeks of study. The results of this study indicate that delayed carbohydrate digestion via the α-glucosidase inhibitor miglitol or other similar agents may be a useful adjunct in the regulation of food intake and in attenuating weight gain in man and animals in addition to their well-established effects as an adjunct in the treatment of impaired glycemic responses in obesity and NIDDM.

The recently emerged coronavirus SARS-COV-2 viral strain that has caused COVID-19 illness is a member of the Coronaviridiae family, and is well known to produce respiratory, gastrointestinal and other illnesses in man and animals.1,2 Although the exact source or origin of the SARS-COV-2 viral strain has not yet been established, the coronavirus strain that causes Covid-19 is also genetically related to some zoonotic viruses isolated from pangolin, bats and camels, and which have previously caused respiratory illness in humans.3–5 Thus, the human infections likely could have occurred from an intermediate animal host via incidental interspecies transmission or other unconfirmed epidemiological origins as is believed to have occurred with the MERS strain. The Coronavirus Sars 2-Cov-19 pandemic first emerged in Wuhan, China on or before January 2020 and spread worldwide exponentially during the Spring to Fall of 2020.2 The newly described viral illness infected millions of people globally by year’s end and has continued into 2021 to the present, during which interval multiple infectious COVID-19 mutations have evolved, some with a more highly infectious potential than that of the initial virus. Continuing outbreaks of the viral mutants have emerged, often seemingly evading immunities formed from immunizations and earlier variants. Thus, the purpose of the present editorial review is to present an overview of the origins and progressive developments in the current coronavirus pandemic and to propose an application of biophotonic and bioelectromagnetic therapy as an often-effective adjunct in the treatment of potentially life threatening viral and microbial illnesses. This brief review paper concludes that biophotonic and bioelectromagnetic therapy (treatment) modalities have been utilized successfully for many years, prior to the development of antimicrobial and antiviral pharmaceutic agents as the current standard of care in common present-day therapies for infectious diseases

The Soufriere Hills Volcano of Montserrat has ancient origins and roared back to life in 1995 wreaking severe havoc and damage to the inhabitants, geography, and ecosystems of the Island. The pyroclastic ash flow reached temperatures of 1500 °F and progressed down the hillsides at speeds of 80 mph, causing incineration and virtual destruction of everything in its path, while the gaseous and particulate laden plume reached altitudes of 35,000 feet, impacting air quality and aircraft navigation. The local health authorities recommended masking and physical protection from any potentially harmful effects from the ash to all residents who remained on Island following the 1995 eruption. Volcanic ash can be an irritant to exposed skin and respiratory surfaces upon contact due in part to the sharp and jagged nature of the microcrystalline particulate matter. In addition, the minute size of the smallest particulate matter can impact deep into the unprotected respiratory tree in humans and animals, potentially causing severe respiratory injury. The composition and physicochemical nature of the ash was largely unknown in 1995 and subsequent years. The current study was designed to determine the geochemical composition of the ash. Samples of ash were collected from 7 locations and water samples from three free flowing creeks in Montserrat and indicated that the creek water was acidic in nature. The mean pH of water was 5.2, while the ash showed abundant levels of Iron, Phosphorus, Calcium, Magnesium, Sodium, Aluminum, and sulfur, in addition to lower concentrations of potassium, boron, copper and zinc and intermediate concentrations of Manganese and was devoid of toxic minerals including lead and mercury. The emergence of acute respiratory issues was not found to exceed similar events in other healthy populations including individuals relocated to the UK. In conclusion, direct human and animal exposure to Montserrat volcanic ash was deemed non-harmful to humans when adequate protective measures including masking and exposure precautions were undertaken, while the rich mineral content of the ash can provide a rich source of micronutrient mineralization to soils and surrounding seawaters and support vigorous revegetation and recovery of affected land and sea zones throughout the island community.