TABLE 1.

Impact of Leptin Treatment in Conditions of Leptin Deficiency and Leptin Excess in Mouse Models and Humans With Metabolic Diseases

	Leptin Levels	Weight	IR	Glucose	TGs	NAFLD	SNS Activity BP*	Energy Intake	Energy Expenditure	Lipid Metabolism†
Animal studies
Ob/ob mice	Extremely low	↓↓↓	↓↓	↓↓	↓↓	↓	↑↑	↓↓↓	↑↑	↑↑
DIO mice	High	↔↓	↔↓	↔↓	↔↓	+/↓	↑	↔↓	↔	NA
Human studies
CLD	Extremely low	↓↓↓	↓	↓	↓	↓	↔‡	↓↓↓	↔§	↑↑
GL	Extremely low	↓	↓↓↓	↓	↓↓↓	↓↓↓	↔↓	↓	↔	↑
PL	Very low	↓	↓↓	↓↓	↓↓	↓↓	↔↓	↓	↔	↑
HALS	Low	↔	↓	↓	↓↓	↔↓	NA	↔	↔	NA
Lean with Low % of body fat due to exercise	Low	↓	NA	↔	NA	NA	↔	↓	↔	↑
Common obesity	High	↔	↔	↔	↔	↔	↔	↔	↔	↔

The arrows indicate the impact of leptin treatment.

^*SNS activity has been assessed in human clinical studies indirectly, by measuring arterial blood pressure and heart rate.

^†Lipid metabolism may refer either to increased lipolysis or reduced de novo lipogenesis, or generally to alterations in circulating lipids.

^‡One study reported transient increase of blood pressure and heart rate with short-term leptin treatment but no effect in the longer term and after weight loss (141).

^§Leptin therapy does not induce energy expenditure but prevents the decrease in metabolic rate that results by weight loss.

BP = blood pressure; CLD = congenital leptin deficiency; DIO = diet-induced obese; GL = generalized lipodystrophy; HALS = human immunodeficiency virus-associated lipodystrophy syndrome; IR = insulin resistance; NA = not available; PL = partial lipodystrophy; SNS = sympathetic nervous system; TG = triglyceride.