Table 1.

Major hormone receptor pathways capable of promoting adipogenesis.

Receptor	Activity	In vitro effects	In vivo effects	Epidemiological effects
PPARγ	Agonism	Promotes adipocyte differentiation, also some promotion of pre-adipocyte proliferation	Increased adipose fat deposition, body weights	Increased body weights, reverse hyperglycemia/treat diabetes
PPARβ/δ	Agonism	Promotes adipocyte differentiation	Activation improves lipid profiles, depletes lipid accumulation, increases resistance to diet-induced obesity	PPARβ/δ agonists reduce LDL cholesterol, triglycerides, insulin, and increase HDL cholesterol*
PPARα	Agonism	Promotes adipocyte differentiation	Activation improves hyperinsulinemia and hyperglycemia, reduces weight and adiposity	PPARα agonists reduce serum triglycerides and LDL cholesterol, increase HDL cholesterol
RXRα	Agonism	Promotes adipocyte lineage commitment, adipocyte differentiation	Ablated RXR mice are resistant to diet/chemical-induced obesity	RXR agonists increase plasma triglycerides, cholesterol, decreased thyroid hormones
GR	Agonism	Promotes adipocyte differentiation, pre-adipocyte proliferation	GR knock-down mice are resistant to diet-induced obesity, have improved insulin sensitivity and glucose tolerance, and increased energy expenditure	Excess glucocorticoids associated with increased weight, adiposity, and decreased glucose tolerance/insulin sensitivity
TR	Antagonism	Promotes adipocyte differentiation	TR null mice exhibit increased adipogenesis	Low thyroid hormone levels promote weight gain, high levels promote weight loss
ER	Agonism	Inhibits adipocyte differentiation, promotes pre-adipocyte proliferation	ERKO mice exhibit increased adiposity	Decreased estrogen in menopause associated with increased abdominal obesity
AR	Antagonism	Promotes adipocyte differentiation, no effect on pre-adipocyte proliferation	AR agonism has anti-adipogenic effects in rodents	Low androgen levels associated with increased abdominal obesity, reversed with supplementation
LXR	Agonism	Promotes adipocyte differentiation, pre-adipocyte proliferation	LXR knockout mice exhibit less adipose and are glucose-intolerant; agonist treatment reduces energy expenditure	LXR agonist treatments increase triglycerides, cholesterol, and other negative molecular markers
PXR	Agonism	Promotes adipocyte differentiation	PXR ablation inhibits diet-induced obesity, insulin resistance, and fatty liver disease; agonist treatment promotes adiposity in mice	PXR agonist treatments reported to induce hyperglycemia and increase diabetes risk
CAR	Agonism	Promotes adipocyte differentiation	CAR agonist treatment enhances insulin sensitivity, improves glucose and lipid metabolism, reverses diet-induced obesity	CAR agonist treatment decreases plasma glucose and improves insulin sensitivity
FXR	Agonism	Agonists induce adipocyte differentiation, antagonists reverse	FXR agonist induces weight gain and glucose intolerance in mice	FXR agonist treatments promote reduced lipid accumulation and increased glucose uptake, reduced HDL and increased LDL cholesterol, improved insulin sensitivity
InsR	Agonism	Promotes adipocyte differentiation, triglyceride accumulation	Increased weight gain and glucose intolerance	Insulin supplementation promote increased weight gain, cholesterol, and blood pressure
IGFR	Agonism	Promotes adipocyte differentiation, triglyceride accumulation	Increased weight gain and glucose intolerance	Increased weight gain, triglycerides

Descriptive effects for several major hormone receptor pathways that influence the process of adipogenesis and weight maintenance. Summarized evidence is provided for direction of effects, as well as in vitro, in vivo, and human epidemiological evidence. References and more detailed descriptions can be found within the relevant subsections of the manuscript, within section Nuclear Receptor Mechanisms Mediating Metabolic Disruption.

^*Due to lack of specific, potent, and available ligands, there is minimal reported work in humans. Summarized work describes effects observed in monkey models following treatment with receptor-specific agonists.