DIETARY FACTORS MITIGATING REDUCED SLEEP-ASSOCIATED OBESITY

• Sponsoring Institution: National Institute of Food and Agriculture
• Project Status: COMPLETE
• Funding Source: HATCH
• Reporting Frequency: Annual
• Accession No.: 0228941
• Project Start Date: Oct 1, 2012
• Project End Date: Sep 30, 2017
• Program Code: [(N/A)]- (N/A)

Recipient Organization
UNIVERSITY OF ARIZONA
888 N EUCLID AVE
TUCSON,AZ 85719-4824

Performing Department
Nutritional Sciences

Non Technical Summary
The national incidence of insufficient sleep or poor sleep quality parallels rising rates of obesity and thus underscores efforts to reduce both pathologies, which in will improve livelihood for all of Arizona. Among adults, the prevalence of obesity in Arizona has more than doubled since 1990. Currently 38.3% and 26.5% of adults were overweight or obese, respectively, and 38.3% of adults had insufficient sleep for at least 14 days during the preceding month. Even more alarming are data showing that the prevalence of obesity among young persons in Arizona is greater than the national average (18-24 year olds in Arizona = 23.0% compared to the national average of 16.2%). Based on these data, one can predict that incidence of obesity and chronic insufficient sleep will increase in Arizona based on the current economic climate and rates of obesity among young persons. Behavioral and therapeutic modalities are desperately needed to curtail rates of obesity and insufficient sleep and prevent obesity-associated comorbidities. Despite evidence linking dysfunctional sleep and obesity, the dietary and neural mechanisms underlying weight gain exacerbated by reduced sleep quality are unknown. Data implicate brain orexin signaling pathways are involved yet mechanistic studies are still needed. Currently, no animal model exists to study role of diet and the neural mechanisms underlying sleep associated-obesity. Understanding the role of diet and central mechanisms will aid in development of modalities to treat reduced sleep quality-associated obesity. Therefore, completing the proposed studies will provide a foundation for human translational studies by identifying dietary behaviors and neural mechanisms of dysfunctional sleep prior to the development of obesity and biomarkers. These studies will guide novel therapies that will prevent future weight gain and promote overall health and economic well-being in Arizona.

Animal Health Component

(N/A)

Research Effort Categories

Basic

(N/A)

Applied

(N/A)

Developmental

(N/A)

Classification

Knowledge Area (KA)	Subject of Investigation (SOI)	Field of Science (FOS)	Percent
724	3840	1010	100%

Knowledge Area
724 - Healthy Lifestyle;

Subject Of Investigation
3840 - Laboratory animals;

Field Of Science
1010 - Nutrition and metabolism;

Keywords

sleep

obesity

brain

rodent

Goals / Objectives
The long-term goal is to delineate the role of diet and the neural mechanisms underlying reduced sleep quality associated obesity, which will guide therapeutic interventions to improve overall health. The objectives are first to measure sleep/wake states, SPA, energy expenditure, and brain orexin activity in young (pre-obese), adult (obese), and age-matched OR rats fed a low or high-fat diet. The second objective is to determine if OXA therapy improves sleep quality and reduces body weight gain exacerbated by high fat-diet feeding. For the first objective, I expect that pre-obese and obese rats will have reduced sleep quality, SPA and energy expenditure, and brain orexin receptor mRNA relative to age-matched OR rats. High fat diet will further reduce SPA, sleep and energy expenditure and gene expression, however, OR rats will have a lower reduction. I expect that sleep quality will be positively correlated with SPA, energy expenditure and orexin mRNA, and that OR rats will have better sleep quality than obese rats. Based on our previous report showing phenotypic differences in SPA throughout the lifespan (Teske, Billington et al. 2011), I expect that SPA and energy expenditure will differ before and after the onset of obesity. For the second objective, I expect that OXA will reduce body weight, improve sleep quality, increase wakefulness (duration of wake), and increase SPA and energy expenditure. I expect that a greater reduction in body weight will be associated with a greater increase in SPA and energy expenditure and a greater improvement in sleep quality. Finally, I expect that the change in level of sleep quality will be positively correlated with the change in the level of SPA and energy expenditure.

Project Methods
For objective one, EEG/EMG transmitters will be surgically implanted in 2 and 5 month old male Sprague-Dawley and age-matched OR rats. Following recovery for surgery and acclimation to testing chambers, rodents will be fed either a low or high fat diet. Then SPA, energy expenditure, and EEG/EMG for sleep states will recorded simultaneously and continuously for 24 h. Food intake and body weight will be measured daily. EEG/EMG wave forms will be manually scored into sleep/wake behavioral states. Rodents will then be sacrificed, and orexin and its receptors in brain areas involved in sleep and energy balance regulation will be quantified by real-time RT-PCR. Data will be analyzed Anova to determine diet and group differences. For objective two, rodents will be implanted with transmitters and a cannula for future neuropeptide administartion. Following recovery, baseline response to orexin A (OXA) will be determined. Then rats will be randomly divided into two treatment groups (OXA-treated or control) per diet (low or high fat) to yield four groups, based on their baseline response to OXA. OXA or vehicle-control will be administered daily for ten days. Body weight, 24 h SPA, EEG/EMG, energy expenditure and food intake measurements will be determined after the ten-day treatment period. Data will be analyzed by Anova to determine if diet and OXA treatment reduced body weight, improved sleep quality, reduced sleep and increased SPA and energy expenditure.

Progress 10/01/12 to 09/30/17

Outputs
Target Audience: Nothing Reported Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?Provided research experiences for 42 individuals (4 high school students, 20 undergraduate students, 13 master's degree students, 2 international scholars and 3 doctoral students) and provided employment for 2 employees. How have the results been disseminated to communities of interest?Conference presentations What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? Determined that sleep disruption reduced energy expenditure in a female rodent model of sleep disruption-induced obesity.

Publications

• Type: Journal Articles Status: Published Year Published: 2017 Citation: 1. Coborn JE, Houser MA, Perez-Leighton CE, Teske, JA Role of sex and the environment in moderating weight gain due to inadequate sleep. 2017. Current Obesity Reports. 6(4):397-404. Epub 2017 Nov. 28.
• Type: Journal Articles Status: Published Year Published: 2017 Citation: 2. Kotz CM, Perez-Leighton CE, Teske JA, Billington CJ. Spontaneous Physical Activity Defends Against Obesity. 2017. Current Obesity Reports. 6(4):362-370. Epub 2017 Nov. 3.
• Type: Journal Articles Status: Published Year Published: 2017 Citation: 3. Mella R, Schmidt C, Romagnoli P, Teske JA, Perez-Leighton CE. The food environment, preference and experience modulate the effects of Exendin-4 on food intake and reward. 2017. Obesity. 25(11):1844-1851. Epub 2017 Nov 1.
• Type: Journal Articles Status: Published Year Published: 2017 Citation: 4. DePorter DP, Coborn JE, Teske, JA. Partial sleep deprivation reduces the efficacy of orexin-A in the ventrolateral preoptic area to stimulate physical activity and energy expenditure. 2017. Obesity (Silver Spring). 25(10):1716-1722. Epub 2017 August 17.
• Type: Journal Articles Status: Published Year Published: 2017 Citation: 5. Coborn JE, Deporter DP, Mavanji, V, Sinton CM, Billington CJ, Kotz CM, Teske, JA. Role of orexin A in the ventrolateral preoptic area on components of total energy expenditure. 2017.International Journal of Obesity. 41(8):1256-1262. Epub 2017 April 10.
• Type: Journal Articles Status: Published Year Published: 2017 Citation: 6. Parrish JB and Teske JA. Acute partial sleep deprivation due to environmental noise increases weight gain by reducing energy expenditure in rodents. 2017. Obesity (Silver Spring) Jan;25(1):141-146. Epub 2016 November 29.

Progress 10/01/16 to 09/30/17

Outputs
Target Audience: Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?Provided research experiences for 42 individuals (4 high school students, 20 undergraduate students, 13 master's degree students, 2 international scholars and 3 doctoral students) and provided employment for 2 employees. How have the results been disseminated to communities of interest?Conference presentations What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? Determined that sleep disruption reduced energy expenditure in a female rodent model of sleep disruption-induced obesity

Publications

• Type: Journal Articles Status: Published Year Published: 2017 Citation: 1. Coborn JE, Houser MA, Perez-Leighton CE, Teske, JA Role of sex and the environment in moderating weight gain due to inadequate sleep. 2017. Current Obesity Reports. 6(4):397-404. Epub 2017 Nov. 28.
• Type: Journal Articles Status: Published Year Published: 2017 Citation: 2. Kotz CM, Perez-Leighton CE, Teske JA, Billington CJ. Spontaneous Physical Activity Defends Against Obesity. 2017. Current Obesity Reports. 6(4):362-370. Epub 2017 Nov. 3
• Type: Journal Articles Status: Published Year Published: 2017 Citation: 3. Mella R, Schmidt C, Romagnoli P, Teske JA, Perez-Leighton CE. The food environment, preference and experience modulate the effects of Exendin-4 on food intake and reward. 2017. Obesity. 25(11):1844-1851. Epub 2017 Nov 1.
• Type: Journal Articles Status: Published Year Published: 2017 Citation: 4. DePorter DP, Coborn JE, Teske, JA. Partial sleep deprivation reduces the efficacy of orexin-A in the ventrolateral preoptic area to stimulate physical activity and energy expenditure. 2017. Obesity (Silver Spring). 25(10):1716-1722. Epub 2017 August 17.
• Type: Journal Articles Status: Published Year Published: 2017 Citation: 5. Coborn JE, Deporter DP, Mavanji, V, Sinton CM, Billington CJ, Kotz CM, Teske, JA. Role of orexin A in the ventrolateral preoptic area on components of total energy expenditure. 2017.International Journal of Obesity. 41(8):1256-1262. Epub 2017 April 10.
• Type: Journal Articles Status: Published Year Published: 2017 Citation: 6. Parrish JB and Teske JA. Acute partial sleep deprivation due to environmental noise increases weight gain by reducing energy expenditure in rodents. 2017. Obesity (Silver Spring) Jan;25(1):141-146. Epub 2016 November 29.

Progress 10/01/15 to 09/30/16

Outputs
Target Audience:Lay audience, non-profits, students (high school, undergraduates, graduate) and international scholars. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?Training and professional development to students (high school, undergraduates, graduate) and internationals scholars. How have the results been disseminated to communities of interest?Presentations to local non-profits and children/parents interested in science. What do you plan to do during the next reporting period to accomplish the goals?Determine estrogen dependent and independent mechanisms regulating feeding due to sleep loss.

Impacts
What was accomplished under these goals? Developed model for women who gain weight due to sleep loss.

Publications

• Type: Journal Articles Status: Published Year Published: 2017 Citation: Role of orexin-A in the ventrolateral preoptic area on components of total energy expenditure. Coborn JE, DePorter DP, Mavanji V, Sinton CM, Kotz CM, Billington CJ, Teske JA. Int J Obes (Lond). 2017 May 9. doi: 10.1038/ijo.2017.92. [Epub ahead of print] PMID: 28392556 Similar articles Select item 27896948
• Type: Journal Articles Status: Published Year Published: 2017 Citation: Acute partial sleep deprivation due to environmental noise increases weight gain by reducing energy expenditure in rodents. Parrish JB, Teske JA. Obesity (Silver Spring). 2017 Jan;25(1):141-146. doi: 10.1002/oby.21703. Epub 2016 Nov 29. PMID: 27896948 Similar articles Select item 26951388
• Type: Journal Articles Status: Published Year Published: 2017 Citation: Developing Biomarker Arrays Predicting Sleep and Circadian-Coupled Risks to Health. Mullington JM, Abbott SM, Carroll JE, Davis CJ, Dijk DJ, Dinges DF, Gehrman PR, Ginsburg GS, Gozal D, Haack M, Lim DC, Macrea M, Pack AI, Plante DT, Teske JA, Zee PC. Sleep. 2016 Apr 1;39(4):727-36. doi: 10.5665/sleep.5616. No abstract available. PMID: 26951388 Free PMC Article Similar articles Select item 26870735
• Type: Journal Articles Status: Published Year Published: 2017 Citation: Effect of Housing Types on Growth, Feeding, Physical Activity, and Anxiety-Like Behavior in Male Sprague-Dawley Rats. Teske JA, Perez-Leighton CE, Noble EE, Wang C, Billington CJ, Kotz CM. Front Nutr. 2016 Feb 4;3:4.

Progress 10/01/14 to 09/30/15

Outputs
Target Audience:The target audience included: doctoral students, master's degree students, undergraduate students, high school students, physicians, academians, several lay audiences. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?5 graduate students, 5 undergraduate students and 2 high school students received training and professional development in the form of laboratory rotations, completing a master's degree thesis, presenting posters at poster session at conferences, presenting oral presentations at conferences. How have the results been disseminated to communities of interest?Presented results at local, national and international conferences. Published research in open-access journal What do you plan to do during the next reporting period to accomplish the goals?Explore the role of sleep deprivation to hedonic food intake with rodent models of binge eating and buffet-style diets.

Impacts
What was accomplished under these goals? We performed preliminary studies to refine whether prolonging sleep with 3 prescribed sleep aids sleep affects weight gain through changes in energy intake and energy expenditure. We developed methodology to quantify the energetic cost of REM sleep, non-REM sleep, quiet wake and active wake. We presented our research at two national meetings and I taught a lecture to medical students. I developed course material for an online course.

Publications

• Type: Journal Articles Status: Published Year Published: 2015 Citation: Promotion of Wakefulness and Energy Expenditure by Orexin-A in the Ventrolateral Preoptic Area. Mavanji V, Perez-Leighton CE, Kotz CM, Billington CJ, Parthasarathy S, Sinton CM, Teske JA. Sleep. 2015 Sep 1;38(9):1361-70.
• Type: Journal Articles Status: Published Year Published: 2015 Citation: Sleep disorders, obesity, and aging: the role of orexin. Nixon JP, Mavanji V, Butterick TA, Billington CJ, Kotz CM, Teske JA. Ageing Res Rev. 2015 Mar;20:63-73.

Progress 10/01/13 to 09/30/14

Outputs
Target Audience: The target audience included: doctoral students, master's degree students, undergraduate students, high school students, physicians, academians, several lay audiences. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? 6 graduate students, 6 undergraduate students and 1 high school students received training and professional development in the form of laboratory rotations, completing a master's degree thesis, presenting a poster at a poster session at a conference. How have the results been disseminated to communities of interest? I published papers, gave seminars, guest lectures, trained students in the laboratory and presented research at local and international meetings. What do you plan to do during the next reporting period to accomplish the goals? Determine whether prolonging with commonly prescribed sleep aids sleep mitigates weight gain. Determine how bouts of being awake without moving influences energy expenditure during and after sleep deprivation. In addition, to the past efforts, research will be presented at two national meetings and I will teach a lecture to medical students. I will also develop on online course.

Impacts
What was accomplished under these goals? We quantified the energy expenditure due to REM and NREM sleep, being awake but not moving, physical activity before, during and after acute sleep deprivation. We demonstrated that a reduction in all components of energy expenditure contribute to weight gain during and after acute sleep deprivation. We determined that stress due to sleep deprivation by exposure to environmental noise did not affect weight gain, which suggests that sleep loss due to environmental noise exposure drives the weight gain observed. We determined that the arousal, physical activity and energy expenditure response to the neuropeptide orexin A was diminished after acute or chronic sleep deprivation. This suggests that reduced endogenous drive to expend energy mediated by brain orexin signaling likely contributes to weight gain in response to acute or chronic sleep deprivation.

Publications

• Type: Journal Articles Status: Published Year Published: 2014 Citation: Methodological considerations for measuring spontaneous physical activity in rodents. Teske JA, Perez-Leighton CE, Billington CJ, Kotz CM. Am J Physiol Regul Integr Comp Physiol. 2014 May 15;306(10):R714-21. doi: 10.1152/ajpregu.00479.2013. Epub 2014 Mar 5.
• Type: Journal Articles Status: Accepted Year Published: 2015 Citation: Sleep disorders, obesity, and aging: The role of orexin. Nixon JP, Mavanji V, Butterick TA, Billington CJ, Kotz CM, Teske JA. Ageing Res Rev. 2015 Mar;20C:63-73.
• Type: Journal Articles Status: Accepted Year Published: 2014 Citation: Mavanji V, Perez-Leighton CE, Kotz CM, Billington CJ, Parthasarathy S, Sinton CM, and Teske, JA. Promotion of wakefulness and energy expenditure by orexin A in the ventrolateral preoptic area. Sleep.
• Type: Conference Papers and Presentations Status: Accepted Year Published: 2014 Citation: DePorter, DP, Coborn, JE, Parthasarathy, S and Teske, JA. Sleep deprivation reduces the effectiveness of orexin-A to stimulate physical activity and energy expenditure
• Type: Conference Papers and Presentations Status: Accepted Year Published: 2014 Citation: Barbee, J and Teske, JA. Sleep deprivation increases body weight by reducing energy expenditure. Presented at the Annual Meeting of the Obesity Society, Boston, MA, November 6, 2014.
• Type: Conference Papers and Presentations Status: Accepted Year Published: 2014 Citation: Lighton, J.R.B and Teske, JA. Presented at the Annual Meeting for Recent Advances and Controversies in Measuring Energy Metabolism. Tokyo, Japan, October 2014

Progress 01/01/13 to 09/30/13

Outputs
Target Audience: During this reporting period, the target audience included: doctoral students, master's degree students, undergraduate students, physicians, academians, several lay audiences. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? 2 undergraduate students, 3 master's degree students, 2 doctoral students completed laboratory rotations in my laboratory. One undergraduate student completed an undergraduate honor's thesis. One undergraduate student worked on their undergraduate honor's thesis. How have the results been disseminated to communities of interest? I have published papers, given seminars, given guest lectures and trained students in the laboratory. What do you plan to do during the next reporting period to accomplish the goals? Determine the effect of chronic sleep deprivation on sleep/wake states, spontaneous physical activity, energy expenditure and feeding patterns in young obesity resistant and obese rats. Determine If OXA therapy improves sleep quality and reduces body weight gain exacerbated by sleep deprivation.

Impacts
What was accomplished under these goals? We have measured sleep/wake states, spontaneous physical activity, energy expenditure and feeding patterns in young obesity resistant and obese rats fed a normal diet and quantified the effect of acute sleep deprivation on these endpoints. We determined brain orexin activity in young pre-obese and aged-matched obesity resistant rats and published the results of the study.

Publications

• Type: Journal Articles Status: Published Year Published: 2013 Citation: 1. Teske JA, Billington CJ and Kotz CM. Mechanisms underlying obesity resistance associated with high spontaneous physical activity. Neuroscience. 256: 91-100. 2013. Epub 2013 Oct. 22.
• Type: Journal Articles Status: Published Year Published: 2013 Citation: 2. Teske JA, Perez-Leighton C, Billington CJ and Kotz CM. Role of the locus coerulues in enhanced orexin A-induced spontaneous physical activity in obesity resistant rats. American Journal of Physiology Regulatory, Integrative and Comparative Physiology. 305: R1337-R1345. 2013. Epub 2013 Oct. 2.
• Type: Journal Articles Status: Published Year Published: 2013 Citation: 3. Mavanji V, Teske JA*, Billington CJ and Kotz CM. Partial sleep deprivation by environmental noise increases food intake and body weight in obesity resistant rats. Obesity (Silver Spring). 21(7):1296-405, 2013. Epub 2013 May 13.
• Type: Conference Papers and Presentations Status: Under Review Year Published: 2014 Citation: Rezaimalek, A. and Teske, JA. Orexin A in the ventrolateral preoptic area modulates physical activity in rodents. To be presented at the Annual Meeting for Experimental Biology, San Diego, CA, April 2014.

Progress 01/01/12 to 12/31/12

Outputs
OUTPUTS: Conducted multiple preliminary experiments to determine the dose required to modulate sleep, physical activity and feeding. Facilitated discussion on the interaction between sleep, physical activity and feeding and the application of basic sleep, physical activity and feeding research to clinical medicine. Taught students basic and clinical techniques to measure behaviors that moderate body weight. Mentored undergraduate student s studying the role of sleep deprivation on body weight outcomes. PARTICIPANTS: In addition to myself, two research technicians and 6 students worked on the project. Parter organizations include the Southern Arizona VA Health Care System, Minneapolis VA Health Care System and University of Minnesota. Collaborators from previously mentioned institutions in addition to the University of Arizona provided professional guidance. Undergraduate students, graduate students, and staff received training. TARGET AUDIENCES: Undergraduate students, graduate students and staff were afforded the opportunity to learn and receive training. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
Change in knowledge from experimentas caused modification in methods and techniques and refined skill set. Change in knowledge and adoption of new technique.

Publications

• No publications reported this period