Genetic modulation of the serotonergic pathway: influence on weight reduction and weight maintenance

Abstract

The serotonergic pathway plays a major role in the development of obesity. Its activity can be modulated by the 5-HT transporter-linked polymorphic region in the SLC6A4 gene and the upstream variable number of tandem repeats polymorphism in the MAOA gene. We studied whether these genetic modulations have an influence on weight reduction and weight maintenance in a one-year weight reduction program (OPTIFAST Ò 52). The polymorphisms were genotyped by PCR in a sample of 135 female and 67 male subjects with severe obesity (44 ± 13 years, 122.3 ± 22.2 kg, BMI: 41.7 ± 6.7 kg/m 2 ). The program leads to a total weight loss of 19.9 ± 9.8 kg (16.9 ± 8.3 %) in women and 27.4 ± 13.6 kg (20.4 ± 9.9 %) in men. Anthropometric measurements and blood levels were determined at the start of the program (T0), after the weight reduction phase (T1) and after the subsequent weight maintenance phase at the end of the program (T2). Each polymorphism alone did not significantly influence weight loss or weight maintenance neither in men nor in women. However, women carrying both risk genotypes (SS and 3/3) displayed a lower total weight loss during the program (p = 0.05). This effect derived mainly from difficulties in the weight maintenance phase (p = 0.11), while the weight reduction phase was not affected (p = 0.61). No influence was found in men (p = 0.93). Modulation of the serotonergic pathway by carrying both risk alleles seems to influence success of weight loss programs in women with severe obesity due to problems in stabilizing body weight after weight reduction.

Association of polymorphisms in 5-HTT (SLC6A4) and MAOA genes with measures of obesity in young adults of Portuguese origin

“…Both 5-HTTLPR and MAOA polymorphisms have also been associated with depression in previous studies (Caspi et al, 2003;Bonvicini et al, 2010), and it has been shown that depression is a likely contributor to obesity, particularly in women (Scott et al 2008;Anderson et al 2007). Thus, modulation of the serotonergic pathway by either 5-HTTLPR or MAOA polymorphisms could lead to elevated depression symptoms and ultimately to a reduced weight loss and/or maintenance (Wallmeier et al, 2013).…”

“…Some studies reported that genetic modulation of the serotonergic pathway by polymorphic regions in the serotonin transporter gene (5-HTT; Gene Symbol: SLC6A4; chr: 17q11.2) and in the monoamine oxidase A (MAOA; chr: Xp11.3) gene may play a role in the development of obesity, although results are still controversial (Ducci et al, 2006;Fuemmeler et al, 2008;Sookoian et al, 2007Sookoian et al, , 2008Peralta et al, 2012;Wallmeier et al, 2013). The serotonin transporter 5-HTT is a key molecule in the regulation of serotonin (5-HT) levels via transport of serotonin molecules from the synaptic cleft into presynaptic neurons (Blakely et al, 1994).…”

The effect of lifestyle intervention in obesity on the soluble form of activated leukocyte cell adhesion molecule

“…This study involved 29 subjects (18 women and 11 men) randomly and retrospectively selected from the OPTIFAST®52 program (franchise holder Nestlé Inc., Switzerland) at the University Hospital of Heidelberg. The OPTIFAST®52 program is a 52-week lifestyle intervention that has been previously described [ 10 ]. For the purpose of this study, patient samples and data were studied at three time-points: at the beginning of the program (T0), after 12-week of active weight loss phase through a low-calorie formula-diet (T1) and after 40-week of weight maintenance phase (T2).…”

The association of insertions/deletions (INDELs) and variable number tandem repeats (VNTRs) with obesity and its related traits and complications

“…The primary role of MAOA in regulating catecholamine turnover and hence ultimately influencing their levels indicates that its VNTR is a highly plausible candidate for affecting individual differences in physiological and psychological traits, such as obesity, personality traits, and alcoholism risk [150]. A previous study showed a significant association of MAOA VNTR alleles (either alone or with combination of other gene variants) with weight and BMI in Caucasian populations [98, 151–153], while our unpublished study showed association only with weight; both studies agree that subjects having the lower activity 3R allele tend to have a lower weight than the higher activity 4R allele. Meanwhile, another study showed a significant association of this VNTR with obesity in a mixed-ethnic American population [154], while Dias et al [116] and our unpublished studies showed otherwise.…”