In a stunning study, Sadaf Farooqi found that found a girl who gained weight excessively from 4 months of age, likely because she felt constantly hungry. Treatment with leptin cured the obesity (Farooqi et al 1999). The figure to the left is from a 3 year old boy who weighed 42kg and after leptin administration weighed 32kg at 7 years old (see Farooqi and O'Rahilly 2014). While this particular condition is exceedingly rare, the core genes found to be involved in energy homeostasis are conserved between humans and mice and indeed in all vertebrates including amphibians, birds and fish.
Simply, the hormone leptin is produced in adipose tissue in proportion with fat mass and signals via AgRP and POMC neurons to melanocortin neurons that enough energy is present in the periphery. When we fast, the leptin (from the greek leptos - thin) levels drop and this gets translated by the melanocortin neurons in the hypothalamus of the brain into hunger. Mice that lack leptin for example (the obese mouse strain) are profoundly hyperphagic because the brain constantly thinks that the animal is starving!
However, there are some very divergent life histories represented amongst vertebrates!
From a plethora of studies we know that the biochemical pathways underlying energy homeostasis at a cellular level, meaning gycogenolysis, gluconeogenesis, glycolysis, Krebs cycle, fatty acid oxidation et cetera are incredibly well conserved at the protein level, and "for biology there remains the great and nagging problem of how to explain in mechanistic terms the incredible diversity and obvious adaptedness of living things on this planet" (Hochachka, 1988).
While the genes underlying the control of energy homeostasis are well conserved across all vertebrates, the actual details appear to differ between life histories and species. In companion animals, particularly in dogs there have been studies finding similar pathways (reviewed by Wallis and Raffan, 2020). In farm animals, particularly the involvement of the melanocortin receptor 4 (MC4R) appears to lead to weight gain changes but the relationship is no so immanently evident (Switonski et al., 2013). Research in monotremes finds that the relationship between plasma leptin and body adiposity is weak to non existent (Nicol, 2017). Further, the relationship between leptin and obesity becomes even more tenuous as we start looking into fish (Londraville et al., 2014) or birds (Friedman-Einat and Seroussi, 2019). So what happened and what role do these energy homeostasis genes which are conserved at a genetic level play across vertebrates?
On the flipside of the obesity coin is hunger or the control of hunger. Indeed, during food deprivation the body needs to conserve energy and one mechanism to do this is by decreasing costly processes such as reproduction and growth amongst others. Indeed, during fasting, circulating levels of hormones like growth hormone (GH), follicle stimulating hormone (FSH) and luteinizing hormone (LH) drop together with circulating levels of leptin and in mice, even though animals are fasting the circulating hormone levels can be rescued by central leptin administration (Ahima et al., 1996). In mice as well as humans, leptin is secreted in proportion to body fat and therefore this means that as body fat levels and leptin levels drop, so do GH, FSH and LH and thereby the energy costly processes these hormones mitigate. It is therefore more likely, that leptin mitigates fasting biology and prevents energy expenditure when energy levels are low (Flier and Maratos-Flier, 2017). In this line of thought, Barbara Kahn showed that leptin can activate muscular energy stores in mice (Minokoshi et al., 2002).
In several fish species, leptin levels actually increase in response to fasting and it is feasible that this signal drives energy recruitment in fish (Londraville et al., 2014; Deck et al., 2017).