Effects of acute and chronic food restriction on the insulin-like growth factor axis in the guinea pig A Sohlstro¨m, A Katsman 1 , K L Kind 2 , P A Grant, P C Owens, J S Robinson and J A Owens 1 Department of Obstetrics and Gynaecology, University of Adelaide, South Australia 5005, Australia, 1 Department of Physiology, University of Adelaide, South Australia 5005, Australia and 2 Division of Human Nutrition, CSIRO, PO Box 10041, Gouger Street, Adelaide, South Australia 5000, Australia (Requests for offprints should be addressed to A Sohlstro¨m who is now at Department of Physiology and Pharmacology, Karolinska Institute, S-171 77 Stockholm, Sweden) Abstract The effect of fasting (17–18 h) versus food restriction (70% for 80 13 days) on the IGF–IGF binding protein (BP) axis in female guinea pigs was studied and related to body weight, weight gain and food conversion efficiency. Circulating IGF-I was reduced in the fasted (13%) and food-restricted (50%) animals. IGF-II was only decreased (61%) in the food-restricted group. There was no effect of fasting on IGFBP-1 to -4 while IGFBP-1, -3 and -4 were reduced by 56%, 60% and 44% respectively, and IGFBP-2 increased by 72%, in the food-restricted group. Food restriction reduced the relative sizes of fat depots, spleen, liver, thymus and heart, increased those of adrenals, kidneys, pancreas, gastrointestinal tract, M. Biceps, M. Soleus and brain while those of uterus, lungs, thyroids and M. Gastrocnemius were unchanged. IGFBP-1 and -2 were negatively correlated to weight gain and food con- version efficiency in the ad libitum-fed group, while IGF-I, -II, IGFBP-1, -3 and -4 were positively correlated to body weight, weight gain and food conversion efficiency in the food-restricted group. The results show that acute and chronic food restriction have different consequences for the IGF–IGFBP axis. Furthermore, IGF-II as well as IGF-I are implicated in the control of body weight, weight gain and food conversion efficiency under conditions of restricted nutrition. Finally, IGFBP-1 and -2 may have different roles during chronic undernutrition compared with unrestrained nutrition in adult life. Journal of Endocrinology (1998) 157, 107–114 Introduction Insulin-like growth factors (IGF)-I and -II are important polypeptide growth factors expressed in most tissues in the body but present in their highest concentrations in blood, largely in association with IGF-binding proteins (IGFBPs). The major source of circulating IGFs is supposed to be the liver, but other tissues may also contribute, particularly in larger animals (Ketelslegers et al. 1995). IGFs have meta- bolic, mitogenic and differentiating effects on a wide variety of cell types (Jones & Clemmons 1995). During fasting or chronic food restriction, the concentration of circulating IGF-I is reduced and correlates with growth rate in humans and rodents, indicating an important role for IGF-I in the regulation of growth (Ketelslegers et al. 1995). The expression of IGF-I is considered to be controlled by several hormones but mainly by growth hormone (GH). However, a limited availability of nutri- ents can impair IGF-I gene expression independent of hormonal status (Thissen et al. 1994a), a result which is further supported by studies showing that certain amino acids may have a direct effect on the transcription of the IGF-I gene (Thissen et al. 1994b). Circulating levels of IGF-II are higher than IGF-I throughout life in most species studied except in rats and mice which express very small amounts of IGF-II after birth (Daughaday et al. 1986, Zangger et al. 1987, Donovan et al. 1989, Owens et al. 1991). IGF-II stimu- lates growth of numerous cell lines and tissues, but it has not been strongly linked to animal growth (Cohick & Clemmons 1993, Jones & Clemmons 1995). However, the effects of IGF-II have been mostly studied in rats and mice which do not normally express IGF-II postnatally other than in the central nervous system. Recently, Conlon et al. infused female guinea pigs (1995a) and rats (1995b) with IGF-II and were able to stimulate weight gain and food conversion efficiency in rats but not in guinea pigs. Plasma concentrations of IGF-II seem to be less affected by malnutrition than those of IGF-I. Studies in humans and guinea pigs where a short acute fasting has been applied, have shown minor or no reductions in IGF-II (Merimee et al. 1982, Davenport et al. 1988, Peterkofsky et al. 1991), while studies of severely mal- nourished children indicate that IGF-II concentrations can be reduced by long-term restricted nutrition (Soliman et al. 1986). 107 Journal of Endocrinology (1998) 157, 107–114  1998 Journal of Endocrinology Ltd Printed in Great Britain 0022–0795/98/0157–0107 $08.00/0