Ciliary neurotrophic factor (CNTF) genotype and body composition

Abstract

Exogenous ciliary neurotrophic factor (CNTF) administration causes significant weight loss in both humans and animal models, but the effects of endogenous CNTF and the CNTF null allele on body composition are not fully understood. A recent study in a European cohort demonstrated a significantly higher body weight and body mass index (BMI) in older males homozygous for the CNTF null allele (A/A genotype). We sought to replicate these findings in three cohorts: the Baltimore Longitudinal Study on Aging (BLSA) consisting of 422 adult men and women (19 -90 years); the Study of Osteoporotic Risk in Men (STORM) consisting of 333 older men (50 -84 years); and a third sample obtained by combining older males aged 59-73 years from the BLSA and STORM cohorts (n ¼ 286). In contrast to the European study, we were unable to detect a significant association between CNTF genotype and body weight in the BLSA (P ¼ 0.49), the STORM (P ¼ 0.28), or the combined samples (P ¼ 0.72). There was also no significant association observed between CNTF genotype and BMI in the BLSA (P ¼ 0.59), the STORM (P ¼ 0.34) or the combined (P ¼ 0.56) samples. In addition, we were unable to detect a significant association between CNTF genotype and total body fat (P ¼ 0.95) or fat-free mass (P ¼ 0.86) in the BLSA cohort. Our results do not support an effect of the CNTF null allele on body composition, contrary to previous findings.

The Human Obesity Gene Map: The 2004 Update

“…Among these studies, the most frequent ones were those pertaining to markers of UCP2 (139,140,165,166,167,168,169,170) (eight studies), APOE (171,172,173,174,175,176,177) (seven studies), PPARG (121,175,178,179,180,181) (six studies), ACDC (182,183,184,185,186), ADRB3 (187,188,189,190,191), and GNB3 (192,193,194,195,196) (five studies each), and ACE (195,197,198,199), IL6 (200,201,202,203), IRS1 (204,205,206,207), and LEPR (208,209,210,211) (four studies each). Other markers yielding negative findings were those related to ADRB2 (212), AGT (213,214), APOA4 (215), APOB (216), APOC3 (217), BBS1 (218), BCHE (219), BDKRB2 (220), CAPN10 (221), CCL2 (222), CNTF (223), COL1A1 (224), COMT (225), CRHR2 (23), CRP (226), CYP11B2 (227), CYP17A1 (225), EDN1 (228), ENPP1 (178,229), ESR1 (230), F7 (231), FABP2 (232,233), GHSR (234), GLP1R (235), GPR10 (236), GPX1 (237), GRLN (238), HSD11B1 (239), HTR2C (240…”

Relation of weight maintenance and dietary restraint to peroxisome proliferator–activated receptor γ2, glucocorticoid receptor, and ciliary neurotrophic factor polymorphisms

“…O'Dell et al (17) found that males who were homozygous for this naturally occurring null mutation had significantly higher body weight (BW) and BMI than did those who were not homozygous. Others have reported no association (15,18). Therefore, in the current study, we assessed the possible relations between the GRL, CNTF, and PPAR␥2 genotypes and WM after a period of weight loss.…”

A putative physiological role of hypothalamic CNTF in the control of energy homeostasis

“…Several studies attempted to correlate CNTF genotype and body mass. Except in a report showing that the homozygous null mutation of the CNTF gene is associated to increased body mass in humans [19], no link was found between CNTF gene disruption and body weight [16,20]. However, compensatory mechanisms cannot be excluded.…”

“…Besides, the role of CNTF as an endogenous modulator of energy homeostasis has not been yet determined. Indeed, correlation studies between CNTF gene disruption and body weight in mice or humans provided controversial data [16–20]. However, compensatory pathways cannot be excluded in such genetic approaches [21].…”