Pilot Project to Examine the Effects of Exercise on Nocturnal Lipolysis in Men and Women

The goal of this proof of concept/feasibility study is to use rigorous methodology to explore links between daytime energy status and nocturnal fat metabolism in healthy adults.

Study Overview

• Status: Completed
• Conditions: Healthy

Detailed Description

This primary goal of this pilot project is to obtain preliminary data demonstrating the feasibility of measuring lipolysis and fat oxidation during sleep in adult human subjects using microdialysis, stable isotope labeling techniques, and whole-room indirect calorimetry. The results of this study will be used in grant applications to perform definitive studies using these methods. The long term goal of this line of research is to explore the mechanisms responsible for sex based differences in the effectiveness of physical activity as an approach to weight loss. Previous longitudinal data have shown that in normal weight and obese individuals, for any given increase in physical activity, there is a significantly greater loss of fat mass in men relative to women [Westerterp, 1997]. These data need to be reconciled, however, with the wealth of data demonstrating that during exercise, women release and oxidize fat more readily than men [Horton, 2009; Horton 1998, Moro 2007]. This phenomenon seems counterintuitive, given that men have less body fat than women and are able to lose more body fat than women when beginning a weight loss program [Bjorntorp, 2007]. Recent data suggests a mechanism to explain this paradox. Specifically, in obese subjects, 24-hour fat oxidation increased following a daytime bout of exercise, and this increase occurred in men only and was driven by a significant increase in fat oxidation not during the day but rather during sleep the night following exercise [Bergouignan, 2014]. Since the predominant source of fuel during sleep is free fatty acids (FFA) released from adipose tissue (i.e., lipolysis), it may be that enhanced sleeping lipolysis is a key factor in how exercise stimulates fat oxidation and thus greater fat loss in males vs. females over time.

The primary objective of the proposed study is to demonstrate the feasibility of measuring nocturnal whole-body and regional lipolysis by using stable isotope techniques and microdialysis of subcutaneous abdominal adipose tissue respectively with the long term goal of determining the effects of acute exercise during the daytime on rates of lipolysis at night in men and women. A secondary objective of this study is to determine if nocturnal regional lipolysis measured by microdialysis of subcutaneous abdominal adipose tissue and whole body lipolysis measured by a stable glycerol isotope infusion are related to dietary and whole body fat oxidation measured by stable isotope labelled fatty acid and whole-room calorimetry, respectively. Finally, the study aims to determine if sleep quality parameters measured by EEG and wrist actigraphy correlate with measures of nocturnal fat oxidation and lipolysis (regional and whole body)

• Study Type: Observational
• Enrollment (Actual): 15

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 35 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Healthy Adults

Description

Inclusion Criteria:

• Males and Females, 20-35 years of age
• Sedentary (planned exercise < 3 d/week, < 30 min/session)
• Lifetime maximum BMI of 30 kg/m2
• Weight stable by self-report for at least 2 mo before the study (<5% weight change)
• Habitual sleeping pattern of >7 hours not to exceed 9.25 hours of sleep per night
• Zero to low-moderate caffeine intake (not to exceed 500 mg/d)
• Alcohol use fewer than two standard drinks per day per week for males and one or less drinks per day per week for females.

Exclusion Criteria:

• Current smoker
• Use of any medication that could affect lipid metabolism, insulin signaling, or sleep
• Pregnant women will not be enrolled in the study
• Current or chronic medical/psychiatric conditions
• Shift work or dwelling below Denver altitude (1,600 m) a year prior to testing
• Travel across more than one time zone 3 wk before study
• Abnormal eating patterns identified by interview and eating questionnaire
• Screening positive for illicit drugs
• Chronic health conditions such as diabetes,
• Hyper or hypothyroidism
• Sleep apnea (Apnea-Hypopnea Index >5)
• Renal or liver disease, anemia, or cancer
• Regularly go to sleep after midnight

• One or more of the following out-of-range values measured on a fasting blood sample:

  • glucose > 110 mg/dl,
  • thyroid stimulating hormone <0.5 or >5.0 uU/ml,
  • hemoglobin < 14.5 g/dl men, <12.3 g/dl women,
  • alanine amino transferase > 47 U/l,
  • aspartate aminotransferase > 47 U/l,
  • alkaline phosphatase <39 or >117 U/l, or
  • creatinine >1.1 mg/dl.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Lipolysis	Measured using stable isotope tracers and microdialysis	Overnight (2200h-0700h)
Change in Substrate Oxidation	Measured using whole-room calorimetry	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Sleep Quality	Measured using wrist actigraphy	Overnight (2200h-0700h)
Change in Lipolytic Hormones	Frequent blood sampling to measure growth hormone, cortisol, catecholamines, and other lipolytic hormones	Overnight (2200h-0700h)

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Investigators: Principal Investigator: Daniel Bessesen, MD, University of Colorado, Denver

Publications and helpful links

General Publications

• Westerterp KR, Goran MI. Relationship between physical activity related energy expenditure and body composition: a gender difference. Int J Obes Relat Metab Disord. 1997 Mar;21(3):184-8. doi: 10.1038/sj.ijo.0800385.
• Horton TJ, Dow S, Armstrong M, Donahoo WT. Greater systemic lipolysis in women compared with men during moderate-dose infusion of epinephrine and/or norepinephrine. J Appl Physiol (1985). 2009 Jul;107(1):200-10. doi: 10.1152/japplphysiol.90812.2008. Epub 2009 Apr 30.
• Horton TJ, Pagliassotti MJ, Hobbs K, Hill JO. Fuel metabolism in men and women during and after long-duration exercise. J Appl Physiol (1985). 1998 Nov;85(5):1823-32. doi: 10.1152/jappl.1998.85.5.1823.
• Moro C, Pillard F, de Glisezinski I, Crampes F, Thalamas C, Harant I, Marques MA, Lafontan M, Berlan M. Sex differences in lipolysis-regulating mechanisms in overweight subjects: effect of exercise intensity. Obesity (Silver Spring). 2007 Sep;15(9):2245-55. doi: 10.1038/oby.2007.267.
• Bjorntorp PA. Sex differences in the regulation of energy balance with exercise. Am J Clin Nutr. 1989 May;49(5 Suppl):958-61. doi: 10.1093/ajcn/49.5.958. No abstract available.
• Bergouignan A, Kealey EH, Schmidt SL, Jackman MR, Bessesen DH. Twenty-four hour total and dietary fat oxidation in lean, obese and reduced-obese adults with and without a bout of exercise. PLoS One. 2014 Apr 8;9(4):e94181. doi: 10.1371/journal.pone.0094181. eCollection 2014.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2015
• Primary Completion (Actual): September 1, 2017
• Study Completion (Actual): September 1, 2017

Study Registration Dates

• First Submitted: March 30, 2015
• First Submitted That Met QC Criteria: April 2, 2015
• First Posted (Estimate): April 3, 2015

Study Record Updates

• Last Update Posted (Actual): July 1, 2019
• Last Update Submitted That Met QC Criteria: June 27, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: Volunteers
• Other Study ID Numbers: 13-0359