. Author manuscript; available in PMC: 2019 Aug 10.

Published in final edited form as: Front Biosci (Landmark Ed). 2019 Mar 1;24:890–934. doi: 10.2741/4758

Table 1.

Therapeutic interventions applied to obesity models and the observed effects

Intervention	Model	Effect
Treatment with arginase inhibitor, N^ω-hydroxy-nor-L-arginine (nor-NOHA)	C57BL/6 mice fed high-fat diet (HFD)	Prevented HFD-induced increases in body weight, hepatic metabolic abnormalities (323), endothelial dysfunction (324) and adipose tissue inflammation (314).
	Zucker obese rats	Prevented obesity-induced hypertension and endothelial dysfunction (318).
Treatment with arginase inhibitor, S-(2-boronoethyl)-L-cysteine (BEC)	Zucker obese rats	Prevented obesity-induced hypertension and endothelial dysfunction (318).
Treatment with arginase inhibitor, 2-(S)-amino-6-boronohexanoic acid (ABH)	C57BL/6 mice fed high-fat diet (HFD)	Prevented obesity-induced bone loss (325), endothelial dysfunction, hypertension (73) and visceral adipose tissue (VAT) inflammation (14). No effect on body weight.
Endothelial specific Arginase 1 knockout (eNOS^−/−)	C57BL/6 mice fed high-fat diet (HFD)	Prevented obesity-induced endothelial dysfunction, hypertension (73) and visceral adipose tissue (VAT) inflammation (14). There was no effect on body weight.
Global deletion of Arginase 2°	C57BL/6 mice fed high-fat diet (HFD)	Prevented obesity-induced renal oxidative stress and inflammation (326), endothelial dysfunction (327), hepatic steatosis (150), insulin resistance, adipose tissue inflammation (74), and pancreatic ductal adenocarcinoma growth (328).
Supplement with sepiapterin and L-citrulline; precursor of BH4 (tetrahydrobiopterin) and substrate for L-arginine synthesis, respectively	Db/db mice	Prevented cardiomyopathy in obese T2D mice (329).
L-arginine supplementation (potential mechanism of increased NO availability)	Zucker obese rats	Anti-inflammatory effects in obese rats (330) and decreased macrophage inflammatory response (331).
		Prevented obesity-induced hypertension and endothelial dysfunction (318).
	Healthy patients with metabolic syndrome	Improved endothelial function and glucose metabolism in metabolic syndrome patients (332).
	C57BL/6 mice fed high-fat diet (HFD)	Anti-obesity effects, reduced white fat mass and plasma lipids, increased skeletal muscle and brown fat, insulin sensitivity, and increased energy expenditure (321, 333).
Sodium nitrite treatment	Streptozotocin (STZ)-induced diabetic rats fed HFD	Decreased body weight and induction of white adipose tissue browning (334).
Global iNOS^−/− knockout	Ob/ob obese mice given high dose of insulin via implanted insulin pump	Prevented hyperinsulinemia-induced inflammation, fibrosis and insulin resistance in adipose tissue (335, 336).
Phosphodiesterase-5 inhibitor (Sildenafil)	C57BL/6 mice fed high-fat diet (HFD)	Long term treatment (12 weeks): anti-obesity and insulin sensitizing (337).
	C57BL/6 mice	Short term (7 days): browning of white adipose tissue (338).
Global iNOS^−/− knockout mice	Model of metabolic syndrome - Isolated muscle mitochondria	Lower metabolic activity, reduced mitochondrial density and muscle fatty acid oxidation (339).
Global iNOS^−/− knockout mice supplemented with sodium nitrate	Model of metabolic syndrome	Reduced visceral fat mass, circulating triglyceride and glucose levels (340).
eNOS transgenic mice	C57BL/6 mice fed high-fat diet (HFD)	Enhanced fatty acid oxidation in adipose tissue, resistant to diet induced obesity without affecting insulin resistance (20).