Type
Text
Type
Dissertation
Advisor
Acosta-Martinez, Maricedes | Lin, Richard Z. | Zong, Wei-Xing. | El-Maghrabi, Raafat
Date
2014-12-01
Keywords
Adipose Tissue, Brown Adipose Tissue, Metabolism, Obesity, PI3-Kinase | Physiology
Department
Department of Physiology and Biophysics.
Language
en_US
Source
This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree.
Identifier
http://hdl.handle.net/11401/76750
Publisher
The Graduate School, Stony Brook University: Stony Brook, NY.
Format
application/pdf
Abstract
Adipose tissue is a highly insulin responsive organ that contributes to metabolic regulation. Insulin resistance in the adipose tissue affects systemic lipid and glucose homeostasis. Phosphoinositide 3-kinase (PI3K) mediates downstream insulin signaling in adipose tissue, but its physiological role in vivo remains unclear. Using Cre recombinase driven by the aP2 promoter, we created mice that lack the class 1A PI3K catalytic subunit p110alpha or p110beta specifically in the white and brown adipose tissue. The loss of p11alpha, not p110beta, resulted in increased adiposity, glucose intolerance and liver steatosis. Mice lacking p110alpha in adipose tissue exhibited a decrease in energy expenditure but no change in food intake or activity as compared to control animals. This low energy expenditure is a consequence of low cellular respiration in the brown adipocytes caused by a decrease in expression of key mitochondrial genes including uncoupling protein-1. We also found that increased bodyweight in male mice lacking adipose-p110alpha is preceded by a delay in puberty onset and corresponds with elevated leptin gene expression in the white adipose tissue suggesting that changes occurring before obesity onset contribute to metabolic impairments with age. These results illustrate a critical role of adipose-p110alpha in the regulation of early juvenile development and adult energy expenditure through modulation of cellular respiration in the brown adipose tissue and suggest that compromised insulin signaling in adipose tissue might be involved in the onset of obesity. | 141 pages
Recommended Citation
Boughton, Victoria Leigh, "Phosphoinositide 3-Kinase (PI3K) p11alpha Catalytic Subunit in Adipose Tissue Regulates Systemic Metabolism" (2014). Stony Brook Theses and Dissertations Collection, 2006-2020 (closed to submissions). 2630.
https://commons.library.stonybrook.edu/stony-brook-theses-and-dissertations-collection/2630