Abstract
Obesity is a growing health concern, as it increases risk for heart disease, hypertension, type 2 diabetes, cancer, COVID-19 related hospitalizations and mortality. However, current weight loss therapies are often associated with psychiatric or cardiovascular side effects or poor tolerability that limit their long-term use. The hypothalamic neuropeptide, oxytocin (OT), mediates a wide range of physiologic actions, which include reproductive behavior, formation of prosocial behaviors and control of body weight. We and others have shown that OT circumvents leptin resistance and elicits weight loss in diet-induced obese rodents and non-human primates by reducing both food intake and increasing energy expenditure (EE). Chronic intranasal OT also elicits promising effects on weight loss in obese humans. This review evaluates the potential use of OT as a therapeutic strategy to treat obesity in rodents, non-human primates, and humans, and identifies potential mechanisms that mediate this effect.
Highlights
Obesity is a growing health concern, as it increases risk for heart disease, hypertension, type 2 diabetes, cancer, COVID-19 related hospitalizations and mortality
Given the current state of the obesity epidemic and lack of highly effective treatment options, this review focuses on OT as an anti-obesity therapy and mechanisms that contribute to these effects in genetically obese (Kublaoui et al, 2008; Tung et al, 2008; Maejima et al, 2011; Morton et al, 2012; Altirriba et al, 2014) and diet-induced obese (DIO) rodents (Deblon et al, 2011; Maejima et al, 2011, 2017; Zhang and Cai, 2011; Zhang et al, 2011; Morton et al, 2012; Edwards et al, 2021b) as well as in DIO non-human primates (Blevins et al, 2015) and obese humans (Zhang et al, 2013; Lawson et al, 2015; Thienel et al, 2016; Hsu et al, 2017) and assesses the translational and therapeutic potential of OT in humans
OT is secreted from axon terminals from parvocellular paraventricular nucleus (PVN) OT neurons that project to the hypothalamic arcuate nucleus (ARC) (Maejima et al, 2014), nucleus accumbens (NAcc) (Ross et al, 2009, prairie voles)/(Knobloch et al, 2012, rats), midbrain ventral tegmental area (VTA) (Shahrokh et al, 2010), hindbrain parabrachial nucleus (PBN) (Ryan et al, 2017), dorsal motor nucleus of the vagus (DMV) (Sawchenko and Swanson, 1982; Rinaman, 1998) nucleus tractus solitarius (NTS) (Sawchenko and Swanson, 1982; Rinaman, 1998; Sutton et al, 2014), and spinal cord (Sawchenko and Swanson, 1982; Sutton et al, 2014)
Summary
The obesity epidemic and its associated complications (Eckel et al, 2005; Cornier et al, 2008; Grundy, 2008) increase the risk for cardiovascular disease, cancer, type 2 diabetes (T2D), and death, including that from COVID-19 (Gao et al, 2020; Guo et al, 2020; Jordan et al, 2020; Michalakis and Ilias, 2020; Targher et al, 2020; Zhou et al, 2020) and has become a major health concern (Smyth and Heron, 2006). Existing findings at least provide indirect evidence in support of a descending PVN to NTS OT projection in a mouse model (Blouet et al, 2009; Matarazzo et al, 2012; Ryan et al, 2017; Wu et al, 2017) and implicate an important role for OTRs within the caudal hindbrain in the control of body weight through reductions of food intake (homeostatic and hedonic) and increases in BAT thermogenesis or core temperature (as surrogate marker of energy expenditure) in both mice (Blouet et al, 2009; Matarazzo et al, 2012; Ryan et al, 2017; Edwards et al, 2021b) and rats (Baskin and Bastian, 2010; Blevins and Ho, 2013; Ho et al, 2014; Ong et al, 2015, 2017; Roberts et al, 2017; Edwards et al, 2021a). In Section “Does Exogenous Oxytocin Increase Energy Expenditure?,” we will review the potential role of energy expenditure in contributing to the effects of OT on weight loss in rodents and non-human primates
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