Obesity has increased significantly in the last five decades, reaching regular numbers of a pandemic (Blüher, 2019). Together with its comorbidities, obesity is now one of the leading causes of death in Western society (González-Muniesa et al., 2017).

The increased food intake and the preference for high-palatability and energy-density foods likely explain the great population weight gain (Rolls, 2007).

The neural circuits that control feeding are involved in homeostatic and hedonic regulation. Although we usually assess these neuronal circuits separately, they share anatomical or functional areas of the central nervous system (Areias and Prada, 2015; Rossi and Stuber, 2018; Volkow et al., 2013). The hypothalamus and the amygdala are examples of two different anatomical regions whose functions overlap in regulating homeostatic and hedonic feeding. Palatable, energy-dense foods activate brain circuits linked to homeostatic and hedonic regulation in these two areas (Hardaway et al., 2019; Yamano et al., 2004).

The central nucleus of the amygdala (CeA) has an essential role in predatory hunting, anxiety, fear, and eating behavior in humans and rodents (Fox et al., 2015; Han et al., 2017; Janak and Tye, 2015). In humans, images of high-calorie foods activated the CeA in obese and overweight individuals compared to a control group (Holsen et al., 2006; Stoeckel et al., 2008). In rodents, several studies highlight the implication of the CeA in modifying feeding behavior (Glass et al., 2000; St Andre and Reilly, 2007; Yamamoto, 2007). In rodents, bilateral lesions of the amygdala increased feeding and body mass. Also, posterodorsal amygdala lesions changed the macronutrient preference (King et al., 1994, 1996).

Recently, CeA gained prominence in the control of hedonic feeding because it contains heterogeneous cell types that express neurotransmitters and neuropeptides known to be involved in the regulation of ingestion (Areias and Prada, 2015; Hardaway et al., 2019).

Like the hypothalamus, evidence suggests that hormones act directly in the CeA to control food consumption (Areias and Prada, 2015; Boghossian et al., 2009; Castro et al., 2013; Mendes et al., 2018; Peters et al., 2023). Recently, a cluster of neurons in the CeA was identified as responsive to ghrelin and fasting-inducing food intake (Peters et al., 2023). Furthermore, another study showed that activating NPY neurons in CeA increases feeding and decreases energy expenditure (Ip et al., 2019). Together, these studies reveal that CeA has similar mechanistic signaling pathways to regulate feeding as the hypothalamus.

AMPK activation in the mediobasal hypothalamus regulates feeding in response to hormones and nutrients (Andersson et al., 2004; Minokoshi et al., 2004; Okamoto et al., 2018). After providing isolated nutrients such as glucose or a mix of nutrients in a chow diet after fasting, AMPK activity decreases, possibly signaling the body to stop eating. In contrast, the hormone ghrelin, which promotes feeding, activates hypothalamic AMPK, inducing hyperphagia (Andersson et al., 2004; Kola et al., 2008; López et al., 2008; Sangiao-Alvarellos et al., 2010).

As described above, all studies showing the role of AMPK-promoting feeding were conducted in the hypothalamus. Considering that CeA has heterogeneous cells that express multiple molecules potentially involved in food regulation, it is unknown whether AMPK is expressed in the CeA or whether AMPK activity in the CeA might impact the control of energy homeostasis. Since the AMPK Thr-172 phosphorylation indirectly characterizes AMPK activity, we hypothesize that AMPK is expressed in CeA and may be phosphorylated in threonine 172, increasing its activity in response to nutrients and hormones and contributing to the regulation of food intake. Thus, we aimed to evaluate the expression and activation of the AMPK signaling in CeA in response to nutrients and hormones and its involvement in feeding regulation.