Human applications of thermogenesis
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Can Thermogenesis be Used to Treat Obesity?
In the previous study, cold-acclimated animals were able to induce adaptive thermogenesis in cold environments. Although the main purpose of adaptive thermogenesis is to keep warm, researchers questioned whether they could use the concept of metabolic inefficiency of BAT thermogenesis to stimulate increases in energy expenditure to lose weight and treat human obesity. This began the journey of using cold-induced adaptive thermogenesis (CIT) in BAT as a possible therapeutic target for obesity.
To determine if this is a practical approach, researchers needed to find out if human BAT were involved in CIT, and if an increase in BAT stores is capable of altering weight. The study by Vigen et al. (2013) monitored CIT in 26 BAT-positive individuals and in 13 BAT-negative individuals (Figure 2a). BAT-positive individuals showed significantly higher CIT activity, indicating that BAT is also involved in adaptive thermogenesis.
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Figure 2. (a) Cold-induced thermogenesis (CIT) in relation to brown adipose tissue. CIT measurements, denoted in percentages, compared between 26 BAT-positive (BAT+) and 13 BAT-negative (BAT-) subjects. CIT is significantly decreased in BAT- subjects compared to BAT+ subjects.
Figure 2. (b) Brown adipose tissue activity in relation to body mass index. BAT activity decreases as BMI increases in a logarithmic fashion. The black dots indicate the study group conducted by Vigen et al., open dots indicated previously performed measurements.
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Clinical Applications
What is the Relationship Between Obesity and T2DM?
Excessive weight has been established as a risk factor in developing T2DM. T2DM is a metabolic disorder that is characterized by hyperglycemia (high blood sugar) and the lack of insulin production as a result of insulin resistance. Obesity is a potential risk factor in developing T2DM.
What are Some Cutting Edge Drugs that can Combat these Diseases?
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Do Humans have BAT?
Yes! Metabolically active BATs make up as much as 5% of our body weight and are mainly found in the neck and upper chest. However, the amount of BAT in humans decreases with age. If we could somehow take advantage of BAT by increasing its amounts, new weight loss agents could be developed to control obesity and diabetes.
What are the Mechanisms of Miglitol that Reduce Body Weight?
To determine if Miglitol induces weight loss in humans, a murine study by Sasaki, et al. (2013) was conducted on the preventative effects of Miglitol in diet-induced obesity. They found that mice on Miglitol exhibited greater weight loss compared to control mice without Miglitol (Figure 3a). All mice were put on a high fat high sugar diet (HFHSD) and no significant changes in food intake or locomotor activity were seen across the mice. This study concluded that weight-loss was due to increased energy expenditure rather than reduced food intake or increased locomotor activity. Essentially, individuals on Miglitol treatment could be expending energy and thus lose weight without having to exercise.
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Figure 3. (a) Mice treated with higher concentrations of miglitol displayed increased weight loss. All mice were put on a high fat high sugar diet (HFHSD) and treated with no miglitol, 400ppm miglitol, and 800ppm miglitol. Mice treated with 800ppm miglitol have the greatest loss of body weight.
Figure 3. (b) Long-term Miglitol treatment increases Ppargc1a and Ucp1 gene expression. Mice on a high fat high sugar diet (HFHSD) were found to to have increased Ppargc1a and Ucp1 gene expression levels in BAT compared to control HFHSD mice that were not given Miglitol.
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