Kisspeptin (KP) is encoded by the
KISS1 gene and is formed as a 154 amino acid protein precursor [
79]. After cleavage, several forms of biologically active kisspeptins are created. The
KISS1 gene and its receptor, GPR54 (known as Kiss1r), were discovered in 1996 and 1999, respectively [
80]. The main product of KISS1 gene is a 54 amino acid protein. However, also other cleavage peptides such as KP10, 13, and 14, bind to the GPR54 receptor with similar high affinities, thereby causing biological effects [
81]. The expression of GPR54 in human tissues as well as in rodents is wide. So far, the expression of GPR54 has been described in different regions of the brain [
82,
83], as well as in numerous peripheral tissues such as liver, pancreas or fat [
84,
85]. Moreover, studies indicate that GPR54 is able to promote adipocytes differentiation and fat accumulation in mice via a MAP kinase pathway [
85].
Kisspeptin has been recognized as an important maturation and reproductive factor acting in the central nervous system. Its expression was also demonstrated in peripheral tissues involved in carbohydrate-lipid metabolism, i.e., in adipose tissue [
86], the liver [
87], and the pancreas. Kisspeptin is the link between reproduction and the body’s energy status. Reproduction is costly in terms of energy consumption, and maturation requires an adequate supply of nutrients. The lack of food and energy leads to fertility disorders and even infertility [
88]. This regulation is based on many mechanisms; however, it seems that kisspeptin is one of the strongest factors [
81]. The influence of Kisspeptin on energy expenditure occurs not only through a direct interaction with is target tissues but also through an effect on the food behavior. The impact on food intake involves the regulation of hypothalamic neuropeptides and neurotransmitters such as neuropeptide Y (NPY). Research performed by Orlando et al. in 2018 showed that KP10 treatment of rat hypothalamic cell line Hypo-E22 resulted in an increased NPY mRNA expression [
89]. Energy metabolism is based on the main energy reservoir—adipose tissue. Research on kisspeptin in the context of adipose tissue is unclear. Both, GPR54 and kisspeptin are expressed herein [
90]. Interestingly, the expression of KP is independent of the hypothalamus but may depend on the sex hormones. It can act locally on adipocytes or on the entire body [
90]. In vitro studies have shown that KP10 enhances lipolysis, which leads to a lower accumulation of TGs in white adipocytes. Additionally, it also reduces glucose uptake, which confirms its action in reducing fat accumulation [
86]. On the other hand, the opposite effect was demonstrated in a model of mice with a lack of the GPR54 receptor. The experiment showed that a lack of GPR54 inhibits the accumulation of TGs, and the growth of adipocytes is caused by a high-fat diet [
85]. KP may also act as regulators of adipokine secretion by adipose tissue. According to the literature, KP reduces the secretion of adiponectin in 3T3-L1 cells [
86], but an increase in the concentration of adiponectin was observed in/after peripheral administration in Rhesus monkey [
91]. Interestingly, kisspeptin is also present in brown adipose tissue. Mice with a global kisspeptin receptor knockout have a higher body weight than mice lacking the receptor only in brown adipose tissue [
92]. Other studies have shown that the effect of kisspeptin in brown adipose tissue differs between males and females [
93]. Undoubtedly, this information needs further analyses to confirm the direction of kisspeptin’s action, both at the level of adipocytes and the whole organism. Another aspect of the body’s energy metabolism is the involvement of kisspeptin in food intake. Dong et al. showed that the intraperitoneal dose of KP10 reduces food intake in the first 4 h after injection. An increase in the level of leptin, resistin and insulin was also observed [
94]. A similar effect in reducing food intake was obtained by Stengel et al., after administering kisspeptin centrally in mice [
95]. The effect of weight loss was also observed by Sahin et al. Female rats treated with kisspeptin were characterized by a lower body weight and a lower concentration of fatty acids in the serum [
96]. External factors also influence the level of kisspeptin. In male mice, obesity and high leptin levels have been shown to reduce the expression of the
GPR54 and
Kiss1 genes [
97]. The decrease in kisspeptin expression in ovaries was also observed in females exposed to a high-fat diet [
98]. The decrease in the expression of KP and its receptor may also be caused by metabolic disorders, such as type 1 diabetes mellitus (DM1) and type 2 diabetes mellitus (DM2) [
84]. However, in humans, it has been confirmed that obesity in women is correlated with a low level of KP in the serum [
99]. The involvement of KP in lipid metabolism is certain. Its action, however, is difficult to explain linearly, and due to its expression in many tissues, it can create a vicious circle in the body’s energy metabolism. More research is needed to clarify the effects kisspeptin achieves in various reproductive and metabolic disorders and how these disorders may affect the levels of kisspeptin in the central system and in peripheral tissues. A brief summary of the function of kisspeptin in adipose tissue metabolism was provided in .