Editing Obesity (section)

==Pathophysiology==
{{Main|Pathophysiology of obesity}}
[[File:Fatmouse.jpg|thumb|upright=1.3|alt=Two white mice both with similar sized ears, black eyes, and pink noses. The body of the mouse on the left, however, is about three times the width of the normal sized mouse on the right.|A comparison of a mouse unable to produce [[leptin]] thus resulting in obesity (left) and a normal mouse (right)]]

Two distinct but related processes are considered to be involved in the development of obesity: sustained positive energy balance (energy intake exceeding energy expenditure) and the resetting of the body weight "set point" at an increased value.<ref name="pmid28898979">{{cite journal| vauthors=Schwartz MW, Seeley RJ, Zeltser LM, Drewnowski A, Ravussin E, Redman LM | display-authors=etal| title=Obesity Pathogenesis: An Endocrine Society Scientific Statement. | journal=Endocr Rev | year= 2017 | volume= 38 | issue= 4 | pages= 267–296 | pmid=28898979 | doi=10.1210/er.2017-00111 | pmc=5546881}}</ref> The second process explains why finding effective obesity treatments has been difficult. While the underlying biology of this process still remains uncertain, research is beginning to clarify the mechanisms.<ref name="pmid28898979"/>

At a biological level, there are many possible [[pathophysiology|pathophysiological]] mechanisms involved in the development and maintenance of obesity.<ref name="flier">{{cite journal | vauthors = Flier JS | title = Obesity wars: molecular progress confronts an expanding epidemic | journal = Cell | volume = 116 | issue = 2 | pages = 337–50 | date = January 2004 | pmid = 14744442 | doi = 10.1016/S0092-8674(03)01081-X | s2cid = 6010027 | type = Review | doi-access = free }}</ref> This field of research had been almost unapproached until the [[leptin]] gene was discovered in 1994 by J. M. Friedman's laboratory.<ref>{{cite journal | vauthors = Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM | title = Positional cloning of the mouse obese gene and its human homologue | journal = Nature | volume = 372 | issue = 6505 | pages = 425–32 | date = December 1994 | pmid = 7984236 | doi = 10.1038/372425a0 | type = Research Support | bibcode = 1994Natur.372..425Z | s2cid = 4359725 }}</ref> While leptin and [[ghrelin]] are produced peripherally, they control appetite through their actions on the [[central nervous system]]. In particular, they and other appetite-related hormones act on the [[hypothalamus]], a region of the brain central to the regulation of food intake and energy expenditure. There are several circuits within the hypothalamus that contribute to its role in integrating appetite, the [[melanocortin]] pathway being the most well understood.<ref name="flier"/> The circuit begins with an area of the hypothalamus, the [[arcuate nucleus]], that has outputs to the [[lateral hypothalamus]] (LH) and [[ventromedial hypothalamus]] (VMH), the brain's feeding and satiety centers, respectively.<ref>{{cite book | vauthors = Boulpaep EL, Boron WF |title=Medical physiology: A cellular and molecular approach |publisher=Saunders |location=Philadelphia |year=2003 |page=1227 |isbn=978-0-7216-3256-8}}</ref>

The arcuate nucleus contains two distinct groups of [[neuron]]s.<ref name="flier"/> The first group coexpresses [[neuropeptide Y]] (NPY) and [[agouti-related peptide]] (AgRP) and has stimulatory inputs to the LH and inhibitory inputs to the VMH. The second group coexpresses [[pro-opiomelanocortin]] (POMC) and [[cocaine- and amphetamine-regulated transcript]] (CART) and has stimulatory inputs to the VMH and inhibitory inputs to the LH. Consequently, NPY/AgRP neurons stimulate feeding and inhibit satiety, while POMC/CART neurons stimulate satiety and inhibit feeding. Both groups of arcuate nucleus neurons are regulated in part by leptin. Leptin inhibits the NPY/AgRP group while stimulating the POMC/CART group. Thus a deficiency in leptin signaling, either via leptin deficiency or leptin resistance, leads to overfeeding and may account for some genetic and acquired forms of obesity.<ref name="flier"/>