Lazaridi, A.V.
(2020)
Identification of factors that stimulate the brown adipose tissue in healthy adults and patients.
PhD thesis, University of Nottingham.
Abstract
Obesity is caused by excess energy intake and/or low energy expenditure which contributes to the onset of many diseases including cardiovascular disease, diabetes and cancer. For this reason, many studies are focusing on the prevention of obesity as it is a crucial public health issue. In mammals, adipose tissue is comprised of white and brown adipose tissue (BAT). Their function differs, as the main role of the white adipose tissue is to store excess energy, whereas BAT can rapidly produce heat when stimulated, thereby, increasing the energy expenditure. Consequently, enhancing BAT activation could be a potential target to prevent and/or reduce obesity.
Many researchers are now exploring ways to activate BAT in adults using expensive techniques that are not readily available for studying both patients and healthy volunteers. These methods, include positron emission tomography/computed tomography scanning and magnetic resonance imaging. However, the non-invasive method of infrared thermography (IRT) has been shown to quantify BAT activation in humans. This is achieved by measuring absolute or relative changes in the main BAT depot, the supraclavicular (SCR) depot.
Acute exposure to either cool water or air can activate BAT, though whether this can be achieved using a more routine intervention is currently unknown. In my first study, I hypothesised that daily cool showers could promote BAT function. Healthy male adults were recruited and baseline BAT temperature measured using IRT, as well as salivary cortisol and a three day food and exercise diary were measured. Then, they were asked to take daily cool showers for three minutes for seven days and then to attend a second IRT session. Following seven days of cool showers, the maximum BAT temperature was decreased whereas the nearby reference temperature was increased. Neither salivary cortisol, resting metabolic rate, nor eating patterns were changed. These findings suggest an indirect change in BAT function.
Another factor that could potentially be used as a therapeutic compound is cannabidiol (CBD), which has been suggested to promote mitochondrial activity in vitro and in vivo and stimulate the expression of brown fat related genes in fat cell lines. It has yet to be determined whether it can promote BAT function in humans and I hypothesised that ingestion of CBD could stimulate BAT. In a second blinded randomised control study, healthy male lean and overweight (OW) adults were randomly allocated to receive either placebo or 582mg of CBD tablets, daily for a period of seven days. Prior and post oral ingestion, I measured BAT using IRT, on the first and last day of the tablets’ administration. Neither acute nor chronic ingestion of CBD, however, had any notable effect on BAT in adult males, who were either OW or of normal body weight.
Prolactin receptors are expressed in brown adipocytes and it has been proposed that prolactin could regulate BAT function. Therefore, in a third study, I hypothesised that BAT function would be increased in patients with hyperprolactinaemia prior to individualised treatment with dopamine agonist tablets. Patients with high serum prolactin concentration were recruited and BAT activity was measured by IRT prior and post treatment. I showed that the serum prolactin was inversely related to maximum BAT temperature prior to any treatment. Additionally, there was a trend for a reduced BAT temperature, whereas reference temperature was significantly decreased. Both these findings suggest that modulating prolactin secretion could potentially affect BAT stimulation.
In my fourth and final study, I explored the feasibility of the IRT application in a clinical setting, by assessing BAT in morbidly obese female patients, after their first clinical appointment. I demonstrated that the IRT technique is acceptable to the patients and body mass index (BMI) was inversely related to BAT activity.
In conclusion, in my thesis it is demonstrated that IRT can be used to assess BAT function in response to various stimuli in both healthy volunteers and patients.
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