Division of Pediatric Endocrinology and Diabetes, Ulm University Hospital, Ulm, Germany,
The Children's Hospital and Institute of Child Health, Lahore, Pakistan.
Obes Facts. 2019;12(4):460-475. doi: 10.1159/000501319. Epub 2019 Jul 29.
Hyperleptinemia is supposed to play a causal role in the development of obesity-associated hypertension, possibly via increased sympathetic tone. Hence patients with congenital leptin deficiency should be hypotensive and their low blood pressure should increase under leptin substitution.
To test this assumption, we examined ambulatory blood pressure, resting heart rate, Schellong test results, cold pressor test results, heart rate variability, catecholamine metabolites, and aldosterone levels in 6 patients with congenital leptin deficiency before as well as 2-7 days and 7-14 months after the start of leptin substitution. Ambulatory blood pressure was also examined in 3 patients with biallelic disease-causing variants in the leptin receptor gene.
Contrary to our expectations, even before leptin substitution, 1 patient with biallelic leptin receptor gene variants and 4 patients with leptin deficiency had been suffering from hypertension. Short-term substitution with leptin increased blood pressure further in 3 out of 4 patients (from 127.0 ± 11.7 to 133.8 ± 10.6 mm Hg), concomitant with an increase in resting heart rate as well as in heart rate during the Schellong test in all patients (from 87.6 ± 7.7 to 99.9 ± 11.0 bpm, p = 0.031, and from 102.9 ± 13.5 to 115.6 ± 11.3 bpm, p = 0.031, respectively). Furthermore, the systolic blood pressure response during the cold pressor test increased in 4 out of 6 patients. Unexpectedly, catecholamine metabolites and aldosterone levels did not increase. After long-term leptin substitution and weight loss, the resting heart rate decreased in 4 out of 6 patients compared to baseline, and in all patients below the heart rate seen immediately after the start of therapy (from 99.9 ± 11.0 to 81.7 ± 5.4 bpm; p = 0.031).
These results show that obesity-associated hypertension does not depend on the presence of leptin. However, short-term leptin substitution can increase the blood pressure and heart rate in obese humans with leptin deficiency, indicating that leptin plays at least an additive role in obesity-associated hypertension. The mechanisms behind this are not clear but might include an increase in regional sympathetic tone.
高瘦素血症被认为在肥胖相关高血压的发展中起因果作用，可能通过增加交感神经张力。因此，先天性瘦素缺乏症患者的血压应该较低，并且在瘦素替代治疗后血压应该升高。
为了验证这一假设，我们在开始瘦素替代治疗前以及开始后 2-7 天和 7-14 个月，检查了 6 例先天性瘦素缺乏症患者的动态血压、静息心率、Schellong 试验结果、冷加压试验结果、心率变异性、儿茶酚胺代谢产物和醛固酮水平。我们还检查了 3 例具有瘦素受体基因突变的双等位基因突变患者的动态血压。
与我们的预期相反，即使在开始瘦素替代治疗之前，1 例具有双等位基因突变的瘦素受体基因患者和 4 例瘦素缺乏症患者已经患有高血压。短期替代瘦素后，4 例患者中的 3 例（从 127.0 ± 11.7 至 133.8 ± 10.6 mmHg）血压进一步升高，所有患者的静息心率以及 Schellong 试验中的心率均升高（从 87.6 ± 7.7 至 99.9 ± 11.0 bpm，p = 0.031，和从 102.9 ± 13.5 至 115.6 ± 11.3 bpm，p = 0.031）。此外，在 6 例患者中，有 4 例在冷加压试验中的收缩压反应增加。出乎意料的是，儿茶酚胺代谢产物和醛固酮水平没有增加。在长期的瘦素替代治疗和体重减轻后，与基线相比，6 例患者中有 4 例的静息心率下降，所有患者的静息心率均低于治疗开始后立即观察到的心率（从 99.9 ± 11.0 至 81.7 ± 5.4 bpm；p = 0.031）。
这些结果表明，肥胖相关高血压不依赖于瘦素的存在。然而，短期瘦素替代治疗可以增加肥胖症伴瘦素缺乏症患者的血压和心率，表明瘦素至少在肥胖相关高血压中起附加作用。其背后的机制尚不清楚，但可能包括局部交感神经张力增加。
