1. Click to edit Master subtitle style 10/1/2016 Genetic Contribution to Obesity Caitlin Baker Lisa Bakken Gail Feldkamp

2. 10/1/2016 Question: How does protein kinase C β deficiency affect obesity syndrome in ob/ob mice?

3. 10/1/2016 What is Obesity? Having a body mass index (a calculation comparing one's height to their weight) that is over 30

4. 10/1/2016 Clinical Features Obesity is when someone is storing too much fat in their body Obesity affects males and females Obesity can increase the risk of: ◦ Heart Disease ◦ Type 2 Diabetes ◦ Cancer (endometrial, breast and colon) ◦ Hypertension ◦ Stroke ◦ Liver/gall bladder disease ◦ Sleep apnea ◦ Respiratory problems ◦ Osteoporosis ◦ Gynecological problems

5. 10/1/2016 Pathogenesis There are numerous factors that influence how much fat is on one's body: ◦ Food and lifestyle choices ◦ Appetite ◦ Genetic make-up ◦ Adipose tissue homeostasis/atrophy ◦ Leptin serum levels Organism Level ◦ Increased number and size of fat cells in the body

6. 10/1/2016 Pathogenesis Cell Level ◦ Amount of fat is influenced by the rate of food consumption and the rate at which energy is expended/used metabolically ◦ The function of the sympathetic nervous system is to prepare the body for action by increasing energy consumption and blood flow. It's used during times of stress, when it increases energy necessary for vital processes such as heart rate and metabolic rate but decreases the energy used in non-vital functions, such as digestion.

7. 10/1/2016 Pathogenesis Molecular Level Leptin is a hormone derived from adipocyte cells that plays a key role in controlling body fat by suppressing food intake by: ◦ influencing receptors in the hypothalamus ◦ increasing energy usage by increasing thermogenesis (body heat production) in brown adipose tissue and by activating sympathetic activity ◦ Leptin is also known for activating PKC (protein kinase c)

8. 10/1/2016 Protein kinase C β deficiency attenuates obesity syndrome of ob/ob mice by promoting white adipose tissue remodeling Authors: Wei Huang, Rishipal R. Bansode, Naresh Bal, Madhu Mehta, and Kamal D. Mehta

9. 10/1/2016 Previous Studies: Studies indicating importance of leptin in obesity Others?

10. 10/1/2016 Definitions ob gene is involved in the production of leptin PKC β gene: is involved in the production of the serine/threonine protein kinases Leptin is an adipocyte derived hormone required for normal energy homeostasis PKC β kinases that play a key role in signal transduction and regulation of gene expression, in particular it is linked to important aspects of hyperglycemia and plays dual roles in insulin signaling pathways

11. 10/1/2016 Definitions Β -ARs ( β -adrenergic receptors) respond particularly to epinephrine and certain blocking agents. They are subdivided into two basic types: β 1, in myocardium and causing lipolysis and cardiac stimulation, and β 2, in smooth and skeletal muscle and liver and causing bronchodilation and vasodilation. The atypical type β 3 may be involved in lipolysis regulation in adipose tissue. WAT (white adipose tissue) is ‘normal’ fat that stores energy and can result in obese phenotypes BAT (brown adipose tissue) tissues have abundant mitochondria and active oxidative metabolism, which creates a lot of heat in the body and produces a leaner phenotype

12. 10/1/2016 Hypothesis and Goals PKC β deficiency may prevent genetic obesity by remodeling the catabolic functions of adipose tissues. Goals: ◦ To explore the role of leptin in PKC β action ◦ To determine the protective potential of PKC β deficiency on profound obesity

13. 10/1/2016 Methods: The Mice ob/ob (leptin deficient, obese) PKC β-/- (lean, PKCβ deficient) DBKO (leptin and PKCβ deficient)

14. 10/1/2016 Blood and Tissue Collection WAT BAT Liver

15. 10/1/2016 Glucose and Insulin Tests Changes in adiposity are associated with alterations in glucose and insulin homeostasis DBKO mice show improved insulin sensitivity as well as improved glucose metabolism

16. 10/1/2016 Other Tests Oxygen consumption Western Blot Studies Analysis of WAT and BAT Gene Expression Statistical Analysis

17. 10/1/2016 Gene Expression

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19. Conclusion

20. 10/1/2016 References CDC website