Effect of Pinealectomy on Body Weight
Chapter One
Preamble of the Study
Pinealectomy performed for pinealomas (which account for 3% to 8% of brain tumors in children) is followed by dramatically reduced or abolished melatonin secretion. In some cases, melatonin replacement therapy improves insomnia or hypersomnia.
CHAPTER TWO
REVIEW OF RELATED LITERATURE
Introduction
The prevalence of obesity has been rising worldwide for many years and constitutes a major health problem on a global scale (Caballero 2007). Obesity is associated with severe and cost-intensive concomitant diseases, such as cardiac-vascular diseases, and type 2 diabetes. With the exception of bariatric surgery, current obesity treatments lack sufficient long-term efficacy and are complicated by high relapse rates to previous eating habits (Tsai et al. 2005). Additionally, a growing body of research provides evidence for the association of circadian rhythm disruption, altered circadian clock gene expression, bright light at night, impaired sleep and neuroendocrine alterations such as melatonin deficits with both weight gain and obesity (reviewed in (Fonken et al. 2014)). Melatonin is an endogenously synthesized molecule that is secreted by the pineal gland during the night in both nocturnal and diurnal mammals, and interacts with MT1 and MT2 melatonin receptors expressed in the hypothalamic SNC and other brain regions (Reiter 1991). It has been shown in animal models, that exogenous melatonin treatment reduces body mass in obese rodents. This is why some investigators speculate that pineal gland volume (PGV) and melatonin plasma concentration might be involved in the development of obesity (Terron, et al. 2013). However, little is known about the interrelationship between PGV and the pathophysiology of obesity in humans, leaving the question unanswered whether similar mechanisms, such as shown in animals, are prevalent in obese humans. Nevertheless, it has been demonstrated that the melatonin plasma concentration is linearly correlated with solid PGV in healthy subjects (Nolte et al. 2009). Additionally, Nachtigal et al. reported an association between the melatonin plasma concentration and BMI in obese women, but not in normal weight controls or obese men (Nachtigal et al. 2005). However, the reduction of melatonin plasma concentration in obese individuals might be the result of a decrease of functional pineal gland parenchyma Based on these results, we hypothesize that PGV might differ between individuals suffering from obesity and lean healthy controls. Thus, the purpose of this study was to conduct the first comparative highresolution MRI volumetric analyses of the pineal gland in obese individuals, and age and sex matched nonobese participants, which were initially derived from an fMRI-study of our group investigating differences of cue-reactivity and leptin plasma concentration in obese and normal-weight subjects (Grosshans et al. 2012).
In recent years the function of the pineal gland has received increasing attention. In mammals the pineal has been shown to be involved in the regulation of the reproductive system and its modification by external light (for reviews see Wurtman et al., 1968; Kappers, 1969; Quay, 1969 ; Reiter and Sorrentino, 1970; Reiter, 1972). The exact mechanism of pineal action, however, is still unclear. Melatonin is one of the compounds found in the pineal; in mammals it is exclusively produced here. Melatonin has been suggested to be an antigonadotropie hormone of the pineal (Wurtman et al., 1968). Its administration in female laboratory rats resulted in decrease of ovarian weight, delay of puberty and in reduction of oestrns smears in cycling and constant oestrus animals. In male rats, however, the findings have been inconsistent and contradictory, especially with regard to the action of melatonin on testes (Wurtman et al., 1968; Reiter and Fraschini, 1969; Reiter, 1972; Kinson and Lin, 1973). In male weasels, a clear effect of melatonin was reported (Rust and Meyer, 1969) : in winter, implantation prevented the development of testes as well as the change from white winter pelage into brown summer pelage, brought about by long photoperiods, and in summer implanted melatonin caused involution of testes and molt into winter pelage, in spite of long photoperiods. Differences in the findings between rats and weasels could be due to differences in the physiology of rodents and mustelids, or to the fact that the weasel is a seasonal breeder and the laboratory rat is not. Since there is also a paucity of data concerning the influence of melatonin on the sexual physiology of male mammals (Reiter, 1972), it was decided to test the effect of melatonin in males of a seasonally breeding rodent, the Djungarian Hamster. This animal also shows a seasonal change in pelage colour and a marked annual cycle of body weight (Figala et al., 1973).
References
- Sep;59(2):221-9. [2] Amstrup, A.K., Sikjaer, T., Mosekilde, L. & Rejnmark, L. (2013). Melatonin and the skeleton Osteoporos Int. Dec;24(12):2919-27.
- Bao, T., Zeng, L., Yang, K., Li, Y., Ren, F., Zhang, Y. & Gao, Z. (2019). Can Melatonin Improve the Osteopenia of Perimenopausal and Postmenopausal Women? A Meta-Analysis. Int J Endocrinol. 2019 Apr 7;2019: 51516-78.
- Beuerlein, M., Wang, X., Moreau, M., Raso, J., Mahood, J., & Bagnall, K. (2001). Development of scoliosis following pinealectomy in young chickens is not the result of an artifact of the surgical procedure. Microscopy research and technique, 53(1), 81-86.
- Beuerlein, M., Wilson, J., Moreau, M., Raso, V. J., Mahood, J., Wang, X., & Bagnall, K. M. (2001). The critical stage of pinealectomy surgery after which scoliosis is produced in young chickens. Spine, 26(3), 237-240.
- Cardinali, D. P., Ladizesky, M. G., Boggio, V., Cutrera, R. A., & Mautalen, C. (2003). Melatonin effects on bone: experimental facts and clinical perspectives. Journal of pineal research, 34(2), 81-87.
- Chin, H.N., Loh, R., Hong, Y.C. & Gibson-Kueh, S. (2016). Case studies of spinal deformities in ornamental koi, Cyprinus carpio L. Journal of Fish Diseases, 40(1):65-71
- De Vlaming, V. (1980). Effects of pinealectomy and melatonin treatment on growth in the goldfish, Carassius auratus. General and comparative endocrinology, 40(2), 245-250.
- Fischer, T.W., Slominski, A., Tobin, D.J. & Paus, R. (2008). Melatonin and the hair follicle. Journal of Pineal Research. ;44(1):1–15.
- Fjelldal, P.G., Grotmol, S. & Kryvi, H. (2004). Pinealectomy induces malformation of the spine and reduces the mechanical strength of the vertebrae in Atlantic salmon, Salmo salar. Journal of Pineal Research. ;36(2):132–139.
- Francis, T., Ramanathan, N., & Padmavathy, P. (2004). Role of the pineal organ and melatonin in fish. World aquaculture. 21-69.
- Ghosh, J., & Nath, P. (2005). Seasonal effects of melatonin on ovary and plasma gonadotropin and vitellogenin levels in intact and pinealectomized catfish, Clarias batrahus (Linn). Indian Journal of Experimental Biology, 43, 224-232. [13]
- Gitto, E., Pellegrino, S., Gitto, P., Barberi, I. & Reiter, R.J. (2009). Oxidative stress of the newborn in the preand postnatal period and the clinical utility of melatonin. Journal of Pineal Research. ;46(2):128– 139.