East Carolina University Department of Exercise and Sport Science Responses of lipolysis and salivary cortisol to food intake and physical activity in lean and obese children Hershberger, A.M., McCammon M.R., Mahar, M.T., Garry, J., and R.C. Hickner East Carolina University Department of Exercise and Sport Science and Departments of Physiology and Family Medicine

Cortisol and Children • Large group of obese/nonobese prepubertal children • Performed exercise on cycle ergometer at 50% max working capacity • Basal plasma cortisol concentrations were significantly higher in obese children (P < 0.01) • After exercise, cortisol concentrations were significantly higher in obese children at each time point that blood was drawn (P < 0.01) • Increased adrenal function in obese children Garlaschi et al., 1975

Glycerol Release & Obesity Higher glycerol release in obese (p < .05) Lower glycerol release in obese when expressed per kg fat mass (p < .05) Glycerol release decreases in response to food Glycerol release increases in response to exercise Glycerol responses to food & exercise are blunted in obese individuals Bougneres et al. (1997), Coppack et al. (1992), Hickner et al. (1991)

The purpose of this study was to examine the association between salivary cortisol concentrations and rates of intracellular lipolysis determined using a novel microdialysis method in obese and lean children Obese children were hypothesized to have higher concentrations of salivary cortisol and lower rates of subcutaneous abdominal adipose tissue lipolysis than lean children.

Microdialysis Hickner, 2000

Methods

Timeline of Day Visit 7:00 a.m Probe insertion 8:00 9:00 Cortisol #1 10:00 11:00 12:00 p.m. 1:00 2:00 3:00 Fasting blood glycerol/glucose & salivary cortisol Probe insertion Cortisol #1 Cortisol #2 Breakfast 10-10:15 Cortisol #3/dialysate #1 Cortisol #4/dialysate #2 Cortisol #5/dialysate #3 Activity time 12:30 –1:00 Cortisol #6/dialysate #4 Lunch 2-2:15 Cortisol samples at 1:45, 2:45, 3:00, 3:15 Dialysate #5 Dialysate #6

Descriptive Characteristics of Groups Lean Obese Mean ± SD n 14 (7M, 7F) 11 (5M, 6F) Ht. (cm) 136.0 ± 5.0 144.8 ± 6.5a Wt. (kg) 29.4 ± 2.8 57.3 ± 13.8a BMI 15.8 ± 1.3 27.1 ± 5.6 WHR .80 ± .03 .83 ± .03b % BF 15.4 ± 4.3 39.5 ± 7.8 aSignificantly different from lean, p < .05 bSignificantly different from lean, p < .001 BMI & % BF predetermined variables that defined groups

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Conclusions Calculated glycerol release lower in the obese group. Glycerol response to breakfast: larger  in lean than obese. Glycerol response to lunch: similar  in lean and obese. Glycerol response to exercise: larger  in lean than obese. There was no consistent indication that intracellular lipolysis was suppressed by cortisol

The purpose of this study was to determine if there are differences in lipolytic responses to feeding and physical activity between lean (LN) and obese (OB) children, and to determine if these responses are related to the glucocorticoid cortisol.  Fourteen lean and eleven obese children participated in this study of subcutaneous abdominal lipolysis and salivary cortisol response to breakfast and lunch with an intervening exercise session.  Changes in interstitial glycerol (index of lipolysis) and ethanol clearance [index of adipose tissue nutritive blood flow (ATNF)] were measured using microdialysis.  Standard meals were served at 1000 and 1400.  A 20-minute exercise session (140 beats/min heart rate) on the treadmill occurred at 1230. The OB group had higher interstitial glycerol concentrations than the LN group throughout the day (P<0.01). When fasting glycerol release was estimated with the lower fasting adipose tissue nutritive blood flow in the obese group taken into account, glycerol release was lower in the OB than LN group (.645 ± .06 vs. .942 ±  .11 mmol/mL, P<.05).  ATNF responses to feeding and exercise were not different between groups.  Exercise increased interstitial glycerol concentration similarly in the LN and OB groups. Breakfast elicited a decrease in interstitial glycerol concentration in the LN (-33%, P<0.05), but not the OB (-5%, N.S.), group.  However, the decrease in glycerol concentration in response to lunch was similar in LN and OB groups (-41% vs -6%).  The normalization of the antilipolytic response to feeding in the OB group (as seen in the glycerol response to lunch) may have been due to the intervening exercise session.  A significant time*group interaction was evident in the response of salivary cortisol to both breakfast and exercise, although LN and OB groups had similar increases in salivary cortisol in response to lunch.  There was no association between salivary cortisol and the alterations in lipolysis in response to food intake or physical activity. These data suggest that the responses of salivary cortisol and lipolysis are not necessarily linked, but are altered in obesity. Furthermore, prior exercise may improve the antilipolytic response to a meal in obese children.

The Centers for Disease Control and Prevention, using NHANES 1999-2000 data, reported that 15% of children (6-11 yr) and adolescents (12-19 yr) were overweight, based on a body mass index-for-age of ³ the 95th percentile. The health risks often associated with obesity in adults, such as insulin resistance and abnormal plasma lipid profiles, are now being seen in young obese children (1, 2).  Childhood obesity is a strong predictor of adult obesity; therefore, the number of people who will become obese will continue to increase unless childhood obesity is prevented and/or treated (1, 2). Lipolytic, as well as lipid storage, responses to food intake and physical activity are primary factors determining body fat stores.  However, there is little information as to the prevailing rates of lipolysis, or the regulation of lipolysis, in ambulatory children in response to common activities such as food intake and physical activity. Microdialysis is a unique methodology that is ideally suited to investigate this issue in children. Microdialysis can be used to continuously measure interstitial glycerol concentrations and nutritive blood flow (3-8). It is therefore possible to monitor lipolysis in subcutaneous adipose tissue of ambulatory children in a relatively unobtrusive manner using a microdialysis probe attached to a small, portable perfusion pump.  There are no published studies, to our knowledge, of ambulatory microdialysis use in children. Numerous laboratories have reported an association between obesity, particularly central adiposity, and high cortisol concentrations in adults.  One impetus for the study of salivary or plasma cortisol has been the hypothesis that elevated fatty acid release can result in hepatic insulin resistance and increase the risk of the Metabolic Syndrome (9, 10).  Obese adults often have a greater and more prolonged cortisol response to food than lean individuals, particularly after lunch (11-14).  During exercise, cortisol concentrations remain higher in obese than in lean subjects (15).  It has been traditionally thought that cortisol aides in the release and mobilization of fatty acids from muscle and adipose tissue, indicating that the hormone increases lipolysis.  More recently, it has been demonstrated that cortisol may actually suppress, rather than stimulate, lipolysis in fat cells (16).  When fasting glycerol release (rate of lipolysis) is expressed per unit fat mass, a similar or lower glycerol release is apparent in obese compared to lean adults (17, 18).  A reduced suppression of lipolysis by antilipolytic agents has been shown in obese adults, although this poor suppression of lipolysis with obesity is not always seen in subcutaneous fat (17, 19, 20).  Furthermore, stimulation of lipolysis during exercise has been shown to be normal in obese adults (21, 22).  The extent to which lipolytic responses are different in obese and lean children is yet to be determined.         Due to the lack of information on adipose tissue lipolysis and blood flow, as well as the effect of cortisol on lipolysis in children, the purpose of this study was to assess interstitial glycerol concentration, adipose tissue nutritive flow (ATNF) and salivary cortisol responses to food intake and physical activity during an eight-hour study of lean and obese children.