Today’s achievements in systems biology and -omics sciences have facilitated a move from studying individual molecule and tissue to characterizing molecules and cells holistically. Here we make an attempt to discuss the status of a much-needed coherent view that integrates studies on neurobiology and adipobiology as well as those on diabetes and obesity. Globally, cardiometabolic diseases (atherosclerosis, hypertension, type 2 diabetes mellitus, obesity, diabesity, and metabolic syndrome) are most prevalent pathologies at present. In 2000 Astrup and Finer ( Obes Rev 1: 57-59) wrote: “Since type 2 diabetes is obesity dependent, and obesity is the main aetiogical cause of type 2 diabetes, we propose the term 'diabesity' should be adopted” Arguably, the research field of adipobiology has witnessed three major paradigm shifts since the discovery of leptin, an adipose-derived hormone, in 1994. Various neuroendocrine and neurotrophic factors were also included in the increasing list of endocrine and paracrine adipose-secreted signaling proteins collectively designated adipokines. These findings open a novel field of research, neuroadipocrinology, a component of neuroendocrinology. Adipokines, including nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), mediate multiple biological processes such as food intake, immunity, inflammation, memory, mood, and metabolism. The effects on metabolism involve the maintenance of glucose, lipid and energy homeostasis, also cardioprotection, neuroprotection, and ageing. Here we highlight the role of metabotrophic factors (MTF), adipose- and nonadipose-derived biomolecules which mediate these effects. Recent results demonstrate that the circulating and/or tissue levels of some MTF, e.g. adiponectin, NGF, BDNF, glucagon-like protein-1, sirtuin-1, interleukin-10, aquaporin-7, are altered in cardiometabolic diseases, including diabesity. Overall, this may cultivate a novel thinking for diabesity, herein also referred to as Homo diabesus . Key words: adipobiology, adipokines, diabetes, obesity, neurobiology, NGF, BDNF, metabotrophins