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Fig. 2 | Biology of Sex Differences

Fig. 2

From: Obesity: sex and sympathetics

Fig. 2

Relationships between leptin and food intake (inhibitory) and sympathetic nerve activity (SNA; excitatory) in males (left) and females (right), and how these relationships are altered by obesity. Top panel: food intake. In both males and females, a loss or decrease of leptin or leptin receptors increases food intake, producing obesity. Increases in leptin can inhibit food intake, but, in general, high doses are required. In females, leptin’s anorexic effect is enhanced by estradiol (E2). In obese males and females (red lines), the relationship between leptin and food intake is reset to a higher leptin level. In males, increases in leptin no longer inhibit food intake (“leptin resistance”), but blockade of endogenous leptin receptors increases food intake (i.e. endogenous leptin continues to suppress appetite). In females, leptin resistance takes longer to develop, presumably due to suppression of reproductive cycling and decreases in E2. However, whether endogenous leptin continues to suppress food intake in females has not been investigated. Dashed lines indicate hypothetical relationships that require further experimentation. Middle panel: lumbar SNA (LSNA): Leptin increases LSNA in both lean males and females; however, in females, this effect requires proestrus levels of E2. It is unlikely that basal levels of endogenous leptin support (L)SNA in either males or females. In obese males, leptin’s sympathoexcitatory effect is preserved or enhanced and likely contributes to the increased basal SNA observed with obesity in male humans and experimental animals. In contrast, in obese females, suppression of reproductive cycling and estrogen levels likely in parallel suppresses leptin’s sympathoexcitatory effect. This sex difference (enhanced leptin SNA increases in obese males, but reduced leptin effects in obese females), may contribute to the observation that obesity increases SNA in men, but not women. Bottom panel: Summary of known and hypothetical changes in food intake and SNA with increases and decreases in leptin levels or actions in both lean and obese males and females

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