MON-321 AgRP and Food Cravings Decrease with Treatment of Cushing’s Disease

Cushing’s disease (CD) is characterized by chronic exposure to excess glucocorticoids due to an ACTH-producing tumor. Obesity is a prominent feature of CD, although the mechanisms of weight gain have not been completely elucidated. In some patients, obesity persists despite appropriate medical or surgical treatment of CD and normalization of cortisol levels (1). Few studies have followed patients prospectively to understand the effect of CD remission and cortisol normalization on appetite and body weight. Previous studies have not shown a correlation between appetite or food cravings and circulating total peptide YY (PYY), ghrelin, or leptin concentrations, leading to interest in other hormones which may regulate appetite in CD (2). One of these is the neuropeptide Agouti-related protein (AgRP). AgRP is known to promote appetite and decrease energy expenditure by acting as a melanocortin antagonist at the level of the hypothalamus. Plasma AgRP may be elevated in patients with active CD and decreases with normalization of cortisol levels (3). We sought to determine if AgRP may play a role in regulating appetite or food cravings in CD. Plasma AgRP was measured before and prospectively after treatment in 19 patients with CD. Patients completed surveys on appetite and food cravings at these same time points. As expected, AgRP significantly decreased following treatment for CD, with mean AgRP before treatment 128.72 pg/mL (SD 55.41) and mean AgRP after treatment 75.23 pg/mL (SD 23.46). Using a paired t-test, the mean difference of 53.5 pg/mL was significant (p=0.0006). In addition, there were significant decreases in BMI, weight, and waist circumference with CD treatment. We found that plasma AgRP concentrations did not correlate with an 8-question visual analogue scale (VAS) used to assess hunger and satiety. However, treatment of CD significantly reduced Trait Food Craving Questionnaire scores in parallel with circulating AgRP levels using a one-way analysis of variance (p=0.004). Our data suggest that AgRP may play a role in food craving, rather than appetite, in patients with CD. Further research may clarify the relationship between AgRP and food cravings in CD patients before and after treatment. References: 1. Geer et al. Endocrinol Metab Clin North Am. 2014; 43: 75-102. Geer et al. Pituitary. 2016; 19: 117-126.Page-Wilson et al, J Clin Endocrinol Metab. 2019; 104 (3): 961-969.

Effect of browse on post-ingestive energy loss in an Arctic ruminant: implications for muskoxen (Ovibos moschatus) in relation to vegetation change

Shrubs are predicted to dominate tundra with warmer temperatures at northern latitudes. We tested the null hypothesis that addition of browse to a graminoid diet would not alter post-ingestive energy loss in muskoxen ( Ovibos moschatus (Zimmermann, 1780)). Energy losses over 8 h following feeding were used to test our hypothesis. Willows ( Salix alaxensis (Anderss.) Coville, Salix planifolia ssp. pulchra (Cham.) Argus) and birch ( Betula nana L.) (twigs in winter, leaves in summer) were separately mixed at graded levels (0%, 20%, 40%, 60%, and 80%) with chopped hay ( Bromus inermis Leyss.) and fed as single meals to muskoxen. Meals containing ≥60% browse were often partially or completely rejected. Meals containing 20%–60% woody or leafy S. alaxensis or S. p. pulchra resulted in higher energy expenditure than meals of 100% hay. Meals containing 20%–60% woody B. nana tended to decrease energy expenditure relative to 100% hay, while 20%–60% leafy B. nana was similar to 100% hay. We conclude there is an energy cost associated with consuming browse. This cost varies by browse species and type. Since muskoxen tolerated up to 40% browse in the diet, this cost may be within their ecological tolerance. This tolerance has important implications under global warming scenarios.

Morbidity and Infant Development: A Hypothesis

An exploratory assessment was made of the relationship between morbidity during the first six months of life and performance in the Bayley Scales of Mental and Motor Development at eight months of life. The study was conducted in 14 villages of Sui Lin Township, Taiwan, which is a rural agricultural area 180 miles south of Taipei. Prior to the study daily dietary intake of the mothers was estimated to range from 1400 to 2000 kcal and 40 grams of protein. Developmentally the children who were healthy were better off than the children who became ill during the first two trimesters. A striking adverse effect of morbidity was found on both mental and motor scale scores when gastrointestinal and respiratory illness were aggregated. Children without illness plus children who were ill with only one illness in one trimester obtained statistically significantly higher scores than the children who were ill with both types of illness and in both trimesters. These findings were explained as a function of the negative energy balance generally found among ill children in populations where malnutrition is endemic. In search for homeostasis the child reduces activity to decrease energy expenditure, and it is to be expected that the relation of a sick child with its environment may be in jeopardy. A hypothesis regarding the relationship between incidence of morbidity and development is proposed.