using-combination-indirect-calorimetry-infrared-thermography-blood

Using a Combination of Indirect Calorimetry, Infrared Thermography, and Blood Glucose Levels to Measure Brown Adipose Tissue Thermogenesis in Humans

In mammals, brown adipose tissue (BAT) is activated rapidly in response to cold in order to maintain body temperature. Although BAT has been studied ...

La Trobe University

Depression is a common, recurrent, and debilitating illness that has become more prevalent over the past 100 years. This report reviews the etiology and pathophysiology of depression, and explores the role of omega 3 polyunsaturated fatty acids (n-3 PUFA) as a possible treatment. In seeking to understand depression, genetic factors and environmental influences have been extensively investigated. Research has led to several hypotheses for the pathophysiological basis of depression but a definitive pathogenic mechanism, or group thereof, has hitherto remained equivocal. To date, treatment has been based on the monoamine hypothesis and hence, selective serotonin reuptake inhibitors have been the most widely used class of medication. In the last decade, there has been considerable interest in n-3 PUFAs and their role in depression. These fatty acids are critical for development and function of the central nervous system. Increasing evidence from epidemiological, laboratory, and randomized placebo-controlled trials suggests deficiency of dietary n-3 PUFAs may contribute to development of mood disorders, and supplementation with n-3 PUFAs may provide a new treatment option. Conclusions based on systematic reviews and meta-analyses of published trials to date vary. Research into the effects of n-3 PUFAs on depressed mood is limited. Furthermore, results from such have led to conflicting conclusions regarding the efficacy of n-3 PUFAs in affecting reduction in symptoms of depression. PUFAs are generally well tolerated by adults and children although mild gastrointestinal effects are reported. There is mounting evidence to suggest that n-3 PUFAs play a role in depression and deserve greater research efforts.

Omega 3 polyunsaturated fatty acids and the treatment of depression.

An increase in dementia numbers and global trends in population aging across the world prompts the need for new medications to treat the complex biological dysfunctions, such as neurodegeneration associated with dementia. Alzheimer's disease (AD) is the most common form of dementia. Cholinergic signaling, which is important in cognition, is slowly lost in AD, so the first line therapy is to treat symptoms with acetylcholinesterase inhibitors to increase levels of acetylcholine. Out of five available FDA-approved AD medications, donepezil, galantamine and rivastigmine are cholinesterase inhibitors while memantine, a N-methyl d-aspartate (NMDA) receptor antagonist, blocks the effects of high glutamate levels. The fifth medication consists of a combination of donepezil and memantine. Although these medications can reduce and temporarily slow down the symptoms of AD, they cannot stop the damage to the brain from progressing. For a superior therapeutic effect, multi-target drugs are required. Thus, a Multi-Target-Directed Ligand (MTDL) strategy has received more attention by scientists who are attempting to develop hybrid molecules that simultaneously modulate multiple biological targets. This review highlights recent examples of the MTDL approach and fragment based strategy in the rational design of new potential AD medications.

A molecular approach in drug development for Alzheimer's disease.

We examined the influence of linear perspective cues and texture gradients in the perceptual rescaling of stimuli over a highly-salient Ponzo illusion of a corridor. We performed two experiments using the Method of Constant Stimuli where participants judged the size of one of two rings. In experiment 1, one ring was presented in the upper visual-field at the end of the corridor and the other in the lower visual-field at the front of the corridor. The perceived size of the top and bottom rings changed as a function of the availability of linear perspective and textures. In experiment 2, only one ring was presented either at the top or the bottom of the image. The perceived size of the top but not the bottom ring changed as a function of the availability of linear perspective and textures. In both experiments, the effects of the cues were additive. Perceptual rescaling was also stronger for the top compared to the bottom ring. Additional eye-tracking revealed that participants tended to gaze more in the upper than the lower visual-field. These findings indicate that top-down mechanisms provide an important contribution to the Ponzo illusion. Nonetheless, additional maximum likelihood estimation analyses revealed that linear perspective fulfilled a greater contribution in experiment 2, which is suggestive of a bottom-up mechanism. We conclude that both top-down and bottom-up mechanisms play important roles. However, the former seems to fulfil a more prominent role when both stimuli are presented in the image.

The contribution of linear perspective cues and texture gradients in the perceptual rescaling of stimuli inside a Ponzo illusion corridor.

"Only teach me what I need to know!" This commonly heard refrain is often spoken by allied health students while studying preclinical sciences (physiology, anatomy, pharmacology). Here we use a clinical scenario undertaken by second-year Bachelor of Paramedic Practice students of acute coronary syndrome to demonstrate the difference in clinical decision making when using a clinical reasoning approach to treatment rather than relying exclusively on a practice guidelines approach. We hope to demonstrate that understanding basic bioscience concepts, such as the Frank-Starling mechanism and the anatomy and physiology of the autonomic nervous system, are key to providing good clinical care in response to ambiguous patient symptoms. Students who understand these concepts underlying their patient care guideline will make better clinical decisions and better provide quality of care than students who follow the guideline exclusively. We aim this as a practical demonstration of the value of detailed understanding of human bioscience in allied health education. As health care providers transition from "technician" to "practitioner," the key distinguishing feature of the role is the ability to practice independently, using "best judgment" rather than clinical guidelines (alone). Evidence suggests that complex case management requires detailed bioscience understanding.

The difference between a clinical technician and clinical practitioner is in the scope of practice: the need for a bioscience understanding in paramedicine.

Pharmacological interventions to aid weight loss have historically targeted either appetite suppression or increased metabolic rate. Brown adipose tissue (BAT) possesses the capacity to expend energy in a futile cycle, thus increasing basal metabolic rate. In animal models, oestrogen has been implicated in the regulation of body weight, and it is hypothesized that oestrogen is acting by modulating BAT metabolism. A systematic search was performed, to identify research articles implementing in vivo oestrogen-related interventions and reporting outcome measures that provide direct or indirect measures of BAT metabolism. Meta-analyses were conducted where sufficient data were available. The final library of 67 articles were predominantly in rodent models and provided mostly indirect measures of BAT metabolism. Results of this review found that oestrogen's effects on body weight, in rats and possibly mice, are likely facilitated by both metabolic and appetitive mechanisms but are largely only found in ovariectomized models. There is a need for further studies to clarify the potential effects of oestrogen on BAT metabolism in gonad-intact and castrated male animal models.

The capacity for oestrogen to influence obesity through brown adipose tissue thermogenesis in animal models: A systematic review and meta-analysis.

Functional brown adipose tissue (BAT) was identified in adult humans only in 2007 with the use of fluorodeoxyglucose positron emission tomography imaging. Previous studies have demonstrated a negative correlation between obesity and BAT presence in humans. It is proposed that BAT possesses the capacity to increase metabolism and aid weight loss. In rodents it is well established that BAT is stimulated by the sympathetic nervous system with the interscapular BAT being innervated via branches of intercostal nerves. Whilst there is evidence to suggest that BAT possesses beta-3 adrenoceptors, no studies have identified the specific nerve branch that carries sympathetic innervation to BAT in humans. The aim of this study was to identify and trace the peripheral nerve or nerves that innervate human BAT in the supraclavicular region. The posterior triangle region of the neck of cadaveric specimens were dissected in order to identify any peripheral nerve branches piercing and/or terminating in supraclavicular BAT. A previously undescribed branch of the cervical plexus terminating in a supraclavicular adipose depot was identified in all specimens. This was typically an independent branch of the plexus, from the third cervical spinal nerve, but in one specimen was a branch of the supraclavicular nerve. Histological analysis revealed the supraclavicular adipose depot contained tyrosine hydroxylase immunoreactive structures, which likely represent sympathetic axons. This is the first study that identifies a nerve branch to supraclavicular BAT-like tissue. This finding opens new avenues for the investigation of neural regulation of fat metabolism in humans.

Innervation of supraclavicular adipose tissue: A human cadaveric study.

Our objective was to determine whether the influence of linear perspective cues and texture gradients in the perceptual rescaling of stimulus size transfers from one eye to the other. In experiment 1, we systematically added linear perspective cues and texture gradients in a background image of the corridor illusion. To determine whether perceptual size rescaling takes place at earlier or later stages, we tested how the perceived size of top and bottom rings changed under binocular (rings and background presented to both eyes), monocular (rings and background presented to the dominant eye only), and dichoptic (rings and background presented separately to the dominant and nondominant eyes, respectively) viewing conditions. We found differences between viewing conditions in the perceived size of the rings when linear perspective cues, but not texture gradients, were presented. Specifically, linear perspective cues produced a stronger illusion under the monocular compared to the dichoptic viewing condition. Hence, there was partial interocular transfer from the linear perspective cues, suggesting a dominant role of monocular neural populations in mediating the corridor illusion. In experiment 2, we repeated similar procedures with a more traditional Ponzo illusion background. Contrary to findings from experiment 1, there was a full interocular transfer with the presence of the converging lines, suggesting a dominant role of binocular neural populations. We conclude that higher order visual areas, which contain binocular neural populations, are more involved in the perceptual rescaling of size evoked by linear perspective cues in the Ponzo compared to the corridor illusion.

Interocular transfer effects of linear perspective cues and texture gradients in the perceptual rescaling of size.

Our objective was to determine how different spatial frequencies affect the perceptual size rescaling of stimuli in the corridor illusion. Two experiments were performed using the method of constant stimuli. In experiment 1, the task required participants to compare the size of comparison and standard rings displayed over the same background image. ANOVA on the points of subject equality (PSEs) revealed that the perceived size of the top and bottom standard rings changed as a function of the availability of the high, medium, and low spatial frequency information. In experiment 2, the task required participants to compare the size of a comparison ring presented outside of the background image with a standard ring presented inside it. ANOVA on the PSEs revealed that the apparent size of the top and not the bottom standard ring changed depending on the availability of medium spatial frequency information. Eye-tracking revealed that the spatial frequency range of the background image in the periphery affected participants' eye positioning, which may explain why the effects of different spatial frequencies fluctuated across experiments. Nonetheless, when we consider these findings together, we propose that the conceptual understanding of depth plays a more important role in explaining the corridor illusion than the low-level processing of depth information extracted from different spatial frequencies along separate channels.

The conceptual understanding of depth rather than the low-level processing of spatial frequencies drives the corridor illusion.

The impact of brown adipose tissue (BAT) metabolism on understanding energy balance in humans is a relatively new and exciting field of research. The pathogenesis of obesity can be largely explained by an imbalance between caloric intake and energy expenditure, but the underlying mechanisms are far more complex. Traditional non-selective sympathetic activators have been used to artificially elevate energy utilization, or suppress appetite, however undesirable side effects are apparent with the use of these pharmacological interventions. Understanding the role of BAT, in relation to human energy homeostasis has the potential to dramatically offset the energy imbalance associated with obesity. This review discusses paradoxical effects of caffeine on peripheral adenosine receptors and the possible role of adenosine in increasing metabolism is highlighted, with consideration to the potential of central rather than peripheral mechanisms for caffeine mediated BAT thermogenesis and energy expenditure. Research on the complex physiology of adipose tissue, the embryonic lineage and function of the different types of adipocytes is summarized. In addition, the effect of BAT on overall human metabolism and the extent of the associated increase in energy expenditure are discussed. The controversy surrounding the primary β-adrenoceptor involved in human BAT activation is examined, and suggestions as to the lack of translational findings from animal to human physiology and human  to  models are provided. This review compares and distinguishes human and rodent BAT effects, thus developing an understanding of human BAT thermogenesis to aid lifestyle interventions targeting obesity and metabolic syndrome. The focus of this review is on the effect of BAT thermogenesis on overall metabolism, and the potential therapeutic effects of caffeine in increasing metabolism via its effects on BAT.

Effects of Caffeine on Brown Adipose Tissue Thermogenesis and Metabolic Homeostasis: A Review.

This article reviews theoretical and empirical arguments for and against various theories that explain the classic Ponzo illusion and its variants from two different viewpoints concerning the role of perceived depth in size distortions. The first viewpoint argues that all Ponzo-like illusions are driven by perceived depth. The second viewpoint argues that the classic Ponzo illusion is unrelated to depth perception. This review will give special focus to the first viewpoint and consists of three sections. In the first section, the role of the number of pictorial depth cues and previous experience in the strength of all Ponzo-like illusions are discussed. In the second section, we contrast the first viewpoint against the theories that explain the classic Ponzo illusion with mechanisms that are unrelated to depth perception. In the last section, we propose a Bayesian-motivated reconceptualization of Richard Gregory's misapplied size constancy theory that explains Ponzo-variant illusions in terms of prior information and prediction errors. The new account explains why some studies have provided inconsistent evidence for misapplied size constancy theory.

A review on various explanations of Ponzo-like illusions.

5-hydroxytryptamine type 3 (5-HT) receptors are ligand gated ion channels, which clearly distinguish their mode of action from the other G-protein coupled 5-HT or serotonin receptors. 5-HT receptors are well established targets for emesis and gastrointestinal mobility and are used as adjunct targets in treating schizophrenia. However, the distribution of these receptors is wider than the nervous system and there is potential that these additional sites can be targeted to modulate inflammatory and/or metabolic conditions. Recent progress in structural biology and pharmacology of 5-HT receptors have provided profound insights into mechanisms of their action. These advances, combined with insights into clinical relevance of mutations in genes encoding 5-HT subunits and increasing understanding of their implications in patient's predisposition to diseases and response to the treatment, open new avenues for personalized precision medicine. In this review, we recap on the current status of 5-HT receptor-based therapies using a biochemical and physiological perspective. We assess the potential for targeting 5-HT receptors in conditions involving metabolic or inflammatory disorders based on recent findings, underscoring the challenges and limitations of this approach.

Tapping into 5-HT Receptors to Modify Metabolic and Immune Responses.

Using a combination of respiratory gas exchange, infrared thermography, and blood glucose (BGL) analysis, we have investigated the impact of  fruit powder (475 mg) or caffeine (100 mg) on metabolic activity in a placebo controlled (lactose, 100 mg) double-blinded three-way cross-over-design experiment. Metabolic measurements were made on day 1 and day 7 of supplementation in eight adult male participants (22.2 ± 2 years of age, BMI 23 ± 2 kg/m, x̅ ± SD). Participants arrived fasted overnight and were fed a high carbohydrate meal (90 g glucose), raising BGL from fasting baseline (4.4 ± 0.3 mmol/L) to peak BGL (8.5 ± 0.3 mmol/L) 45 min after the meal. Participants consumed the supplement 45 min after the meal, and both caffeine and  fruit powder restored BGL (F  = 2.2,  = 0.02) to near fasting levels within 15 min of supplementation compared to placebo (120 min). In parallel both supplements increased energy expenditure (F  = 175.6,  < 0.001) over the 120-min test period (caffeine = 50.74 ± 2 kcal/kg/min,  fruit = 50.95 ± 1 kcal/kg/min, placebo = 29.34 ± 1 kcal/kg/min). Both caffeine and  fruit powder increased supraclavicular fossa temperature (F  = 32,  < 0.001) on both day 1 and day 7 of testing over the 120-min test period. No statistical difference in core temperature or reference point temperature, mean arterial pressure or heart rate was observed due to supplementation nor was any statistical difference seen between day 1 and day 7 of intervention. This is important for implementing dietary ingredients as potential metabolism increasing supplements. Together the results imply that through dietary supplements such as caffeine and , mechanisms for increasing metabolism can be potentially targeted to improve metabolic homeostasis in people.

Both caffeine and  fruit powder lower blood glucose levels and increase brown adipose tissue temperature in healthy adult males.

[This corrects the article DOI: 10.3389/fphys.2022.870154.].

Corrigendum: Both caffeine and  fruit powder lower blood glucose levels and increase brown adipose tissue temperature in healthy adult males.

The 5-hydroxytryptamine 3 (5-HT) receptor belongs to the pentameric ligand-gated cation channel superfamily. Humans have five different 5-HT receptor subunits: A to E. The 5-HT receptors are located on the cell membrane, but a previous study suggested that mitochondria could also contain A subunits. In this article, we explored the distribution of 5-HT receptor subunits in intracellular and cell-free mitochondria. Organelle prediction software supported the localization of the A and E subunits on the inner membrane of the mitochondria. We transiently transfected HEK293T cells that do not natively express the 5-HT receptor with an epitope and fluorescent protein-tagged 5HT3A and 5HT3E subunits. Fluorescence microscopy and cell fractionation indicated that both subunits, A and E, localized to the mitochondria, while transmission electron microscopy revealed the location of the subunits on the mitochondrial inner membrane, where they could form heteromeric complexes. Cell-free mitochondria isolated from cell culture media colocalized with the fluorescent signal for A subunits. The presence of A and E subunits influenced changes in the membrane potential and mitochondrial oxygen consumption rates upon exposure to serotonin; this was inhibited by pre-treatment with ondansetron. Therefore, it is likely that the 5-HT receptors present on mitochondria directly impact mitochondrial function and that this may have therapeutic implications.

Article	Year
Omega 3 polyunsaturated fatty acids and the treatment of depression. Critical reviews in food science and nutrition\| PubMed ID: 25830700	2017
A molecular approach in drug development for Alzheimer's disease. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie\| PubMed ID: 29990843	2018
The contribution of linear perspective cues and texture gradients in the perceptual rescaling of stimuli inside a Ponzo illusion corridor. PloS one\| PubMed ID: 31600294	2019
The difference between a clinical technician and clinical practitioner is in the scope of practice: the need for a bioscience understanding in paramedicine. Advances in physiology education\| PubMed ID: 31697166	2019
The capacity for oestrogen to influence obesity through brown adipose tissue thermogenesis in animal models: A systematic review and meta-analysis. Obesity science & practice\| PubMed ID: 31890250	2019
Innervation of supraclavicular adipose tissue: A human cadaveric study. PloS one\| PubMed ID: 32702004	2020
Interocular transfer effects of linear perspective cues and texture gradients in the perceptual rescaling of size. Vision research\| PubMed ID: 33276195	2021
The conceptual understanding of depth rather than the low-level processing of spatial frequencies drives the corridor illusion. Vision research\| PubMed ID: 33453548	2021
Effects of Caffeine on Brown Adipose Tissue Thermogenesis and Metabolic Homeostasis: A Review. Frontiers in neuroscience\| PubMed ID: 33613184	2021
A review on various explanations of Ponzo-like illusions. Psychonomic bulletin & review\| PubMed ID: 34613601	2022
Tapping into 5-HT Receptors to Modify Metabolic and Immune Responses. International journal of molecular sciences\| PubMed ID: 34769340	2021
Both caffeine and fruit powder lower blood glucose levels and increase brown adipose tissue temperature in healthy adult males. Frontiers in physiology\| PubMed ID: 36017333	2022
Corrigendum: Both caffeine and fruit powder lower blood glucose levels and increase brown adipose tissue temperature in healthy adult males. Frontiers in physiology\| PubMed ID: 36703937	2022
5-HT Receptors on Mitochondria Influence Mitochondrial Function. International journal of molecular sciences\| PubMed ID: 37176009	2023

Christine Kettle

Biography

JoVE Journal Publications

Other Publications