The imbalance between energy intake and expenditure accompanied by the collapse of mechanisms protecting against the excessive accumulation of energy reserves are considered to be the main causes of obesity . Accordingly, available treatments of obesity are aimed at decreasing calorie intake and/or increasing energy expenditure. However, long-term effects of various non-invasive methods including diets and pharmacotherapy with drugs reducing intestinal ingestion are unsatisfactory. Therefore, bariatric surgery, albeit expensive and potentially harmful, seems to be most effective . Such situation has led to a renewed interest in developing therapeutic approaches which would reduce obesity by increasing energy expenditure. In this minireview the potential role of thermogenesis impairment in development of human obesity as well as possible limitations in the application of thermogenic compounds, namely agonists of the adrenergic receptors beta and thyroid hormone receptors, in obesity treatment are discussed.
In small mammals and in human newborns, non-shivering (adaptive) thermogenesis in brown adipose tissue (BAT) is the most important regulatory mechanism for maintaining body temperature. Energy produced in the BAT mitochondria, due to the oxidation of lipolysis-derived fatty acids, is not used to produce high-energy bonds of adenosine-5’-triphosphate (ATP), but is released as heat, mostly thanks to uncoupling protein 1 (UCP1) .
It was believed that in humans, age progression is accompanied by a complete atrophy of BAT; however, novel methods of imaging led to the identification of BAT stores in several areas of the adult human body, as well as of cells reminding brown adipocytes dispersed within the visceral white adipose tissue (WAT) also known as beige/brite adipocytes .
The prevalence and activity of BAT differ between individuals and are inversely related to age, body mass index (BMI) and the total fat content . BAT activity may vary even in the same subject, depending on cold exposure which is the most powerful and physiological stimulus for its activation. Activity of the cold-stimulated human BAT measured by the uptake of fatty acids and glucose (per gram of tissue) can be higher than in insulin-stimulated skeletal muscle . Apart from its contribution to cold-induced thermogenesis, recent human studies demonstrated that BAT also participates in diet-induced thermogenesis, which may constitute up to 10% of whole body energy expenditure . Therefore, stimulation of thermogenesis in brown adipocytes seems to be an attractive therapeutic pathway in treatment of obesity and related metabolic disorders.
Citation: Kurylowicz A (2015) Stimulation of Thermogenesis via Beta-Adrenergic and Thyroid Hormone Receptors Agonists in Obesity Treatment – Possible Reasons for Therapy Resistance. J Pharmacogenomics Pharmacoproteomics 6:145. doi: 10.4172/2153-0645.1000145