Case Study: Weight loss in a patient with type 2 diabetes: Challenges of diabetes management

Lotfi, Katayoun; Palmer, Kenya D.; Apovian, Caroline M.

doi:10.1002/oby.21095

Cited by 3 publications

(3 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been used as a short-term management of obesity (123) and is approved for short-term (up to 12 weeks) weight management. Like other sympathomimetic agents, phentermine is associated with elevations of blood pressure and heart rate and is not recommended in individuals with preexisting cardiac issues (124). A retrospective cohort study (125) found that cardiovascular disease was rare in individuals taking phentermine for 12 and 24 months, although a slight increase in heart rate was observed.…”

Section: Sympathomimeticsmentioning

confidence: 99%

Opportunities and challenges in the therapeutic activation of human energy expenditure and thermogenesis to manage obesity

Chen

Brychta

Sater

et al. 2020

Journal of Biological Chemistry

View full text Add to dashboard Cite

The current obesity pandemic results from a physiological imbalance in which energy intake chronically exceeds energy expenditure (EE), and prevention and treatment strategies remain generally ineffective. Approaches designed to increase EE have been informed by decades of experiments in rodent models designed to stimulate adaptive thermogenesis, a long-term increase in metabolism, primarily induced by chronic cold exposure. At the cellular level, thermogenesis is achieved through increased rates of futile cycling, which are observed in several systems, most notably the regulated uncoupling of oxidative phosphorylation from ATP generation by uncoupling protein 1, a tissue-specific protein present in mitochondria of brown adipose tissue (BAT). Physiological activation of BAT and other organ thermogenesis occurs through β-adrenergic receptors (AR), and considerable effort over the past 5 decades has been directed toward developing AR agonists capable of safely achieving a net negative energy balance while avoiding unwanted cardiovascular side effects. Recent discoveries of other BAT futile cycles based on creatine and succinate have provided additional targets. Complicating the current and developing pharmacological-, cold-, and exercise-based methods to increase EE is the emerging evidence for strong physiological drives toward restoring lost weight over the long term. Future studies will need to address technical challenges such as how to accurately measure individual tissue thermogenesis in humans; how to safely activate BAT and other organ thermogenesis; and how to sustain a negative energy balance over many years of treatment.

show abstract

Section: Sympathomimeticsmentioning

confidence: 99%

Opportunities and challenges in the therapeutic activation of human energy expenditure and thermogenesis to manage obesity

Chen

Brychta

Sater

et al. 2020

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…TrkB | neurocircuitry | dorsomedial hypothalamus | energy expenditure | feeding I mpairments in energy homeostasis resulting from the compound effects of overeating and sedentary lifestyles have led to a profound increase in the rate of obesity around the world (1). Therapeutic strategies aimed at combating obesity by increasing energy expenditure or decreasing appetite have commonly failed due to counterregulatory mechanisms (2) and adverse side effects on cardiovascular physiology (3)(4)(5). To achieve safe and sustained weight loss, it will be essential to understand the mechanisms that govern and coordinate discrete physiological processes that contribute to energy homeostasis.…”

mentioning

confidence: 99%

Discrete TrkB-expressing neurons of the dorsomedial hypothalamus regulate feeding and thermogenesis

Houtz

Liao

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Mutations in the TrkB neurotrophin receptor lead to profound obesity in humans, and expression of TrkB in the dorsomedial hypothalamus (DMH) is critical for maintaining energy homeostasis. However, the functional implications of TrkB-fexpressing neurons in the DMH (DMHTrkB) on energy expenditure are unclear. Additionally, the neurocircuitry underlying the effect of DMHTrkB neurons on energy homeostasis has not been explored. In this study, we show that activation of DMHTrkB neurons leads to a robust increase in adaptive thermogenesis and energy expenditure without altering heart rate or blood pressure, while silencing DMHTrkB neurons impairs thermogenesis. Furthermore, we reveal neuroanatomically and functionally distinct populations of DMHTrkB neurons that regulate food intake or thermogenesis. Activation of DMHTrkB neurons projecting to the raphe pallidus (RPa) stimulates thermogenesis and increased energy expenditure, whereas DMHTrkB neurons that send collaterals to the paraventricular hypothalamus (PVH) and preoptic area (POA) inhibit feeding. Together, our findings provide evidence that DMHTrkB neuronal activity plays an important role in regulating energy expenditure and delineate distinct neurocircuits that underly the separate effects of DMHTrkB neuronal activity on food intake and thermogenesis.

show abstract

“…Efforts to combat obesity have traditionally focused on lifestyle changes including diet and exercise; however, these strategies have met with limited success in sustaining weight loss (2,3). Additionally, therapeutic strategies aimed at increasing energy expenditure or decreasing appetite have commonly failed due to adverse side effects on cardiovascular physiology (4)(5)(6). In order to achieve safe and sustained weight loss, it will be essential to understand the mechanisms that govern and coordinate discrete physiological processes that contribute to energy homeostasis.…”

Section: Introductionmentioning

confidence: 99%

Discrete TrkB-expressing neurons of the dorsomedial hypothalamus regulate feeding and thermogenesis

Houtz

Liao

2020

Preprint

View full text Add to dashboard Cite

Mutations in the TrkB neurotrophin receptor lead to profound obesity in humans, and expression of TrkB in the dorsomedial hypothalamus (DMH) is critical for maintaining energy homeostasis. However, the functional implications of TrkB-expressing neurons in the DMH (DMHTrkB) on energy expenditure are unclear. Additionally, the neurocircuitry underlying the effect of DMHTrkB neurons on energy homeostasis has not been explored. In this study, we show that activation of DMHTrkB neurons leads to a robust increase in adaptive thermogenesis and energy expenditure without altering heart rate or blood pressure, while silencing DMHTrkB neurons impairs thermogenesis. Furthermore, we reveal neuroanatomically and functionally distinct populations of DMHTrkB neurons that regulate food intake or thermogenesis. Activation of DMHTrkB neurons projecting to the raphe pallidus stimulates thermogenesis and increased energy expenditure, whereas DMHTrkB neurons that send collaterals to the paraventricular hypothalamus and preoptic area inhibit feeding. Together, our findings provide evidence that DMHTrkB neuronal activity plays an important role in regulating energy expenditure and delineate distinct neurocircuits that underly the separate effects of DMHTrkB neuronal activity on food intake and thermogenesis.Brief summaryThis study shows that TrkB-expressing DMH neurons stimulate thermogenesis through projection to raphe pallidus, while inhibiting feeding through collaterals to paraventricular hypothalamus and preoptic area.

show abstract

Case Study: Weight loss in a patient with type 2 diabetes: Challenges of diabetes management

Cited by 3 publications

References 1 publication

Opportunities and challenges in the therapeutic activation of human energy expenditure and thermogenesis to manage obesity

Opportunities and challenges in the therapeutic activation of human energy expenditure and thermogenesis to manage obesity

Discrete TrkB-expressing neurons of the dorsomedial hypothalamus regulate feeding and thermogenesis

Discrete TrkB-expressing neurons of the dorsomedial hypothalamus regulate feeding and thermogenesis

Contact Info

Product

Resources

About