School of Health Sciences, Dedan Kimathi University of Technology, Nyeri, Kenya.
Department of Human Anatomy and Medical Physiology, University of Nairobi, Nairobi, Kenya.
PLoS One. 2024 Feb 28;19(2):e0298752. doi: 10.1371/journal.pone.0298752. eCollection 2024.
This study investigated the interactions between a low protein high calorie (LPHC) diet and an integrase inhibitor-containing antiretroviral drug regimen (INI-CR)in light of evidence suggesting that the initiation of cART in patients with poor nutritional status is a predictor of mortality independent of immune status.
Freshly weaned Sprague Dawley rats (120) were randomized into the standard, LPHC and normal protein high calorie (NPHC) diet groups (n = 40/group) initially for 15 weeks. Thereafter, experimental animals in each diet group were further randomized into four treatment sub-groups (n = 10/group) Control (normal saline), group 1(TDF+3TC+DTG and Tesamorelin), group 2 (TDF+3TC+DTG), and Positive control (AZT+3TC+ATV/r) with treatment and diets combined for 9 weeks. Weekly body weights, fasting blood glucose (FBG), oral glucose tolerance test (OGTT); lipid profiles, liver weights, hepatic triglycerides and adiposity were assessed at week 24.
At week 15, body weights increased between the diet group in phase 1(standard 146 ± 1.64 vs. 273.1 ± 1.56 g), (NPHC, 143.5 ± 2.40 vs. 390.2 ± 4.94 g) and (LPHC, 145.5 ± 2.28 g vs. 398.3 ± 4.89 g) (p< 0.0001). A similar increase was noted in the FBG and OGTT (p< 0.0001). In phase 2, there was an increase in FBG, OGTT, body weights, lipid profile, liver weights, hepatic triglycerides, adiposity and insulin levels in group 2 and positive control in both NPHC and LPHC diet groups (p<0.0001). Growth hormone levels were decreased in Tesamorelin-free group 2 and positive control in both NPHC and LPHC (p< 0.0001).
The obesogenic activities of the LPHC diet exceeded that of the NPHC diet and interacted with both integrase-containing and classical cART drug regimens to reproduce cART associated metabolic dysregulation. The effects were however reversed by co-administration with tesamorelin, a synthetic growth hormone releasing hormone analogue.
本研究旨在探讨低蛋白高热量（LPHC）饮食与包含整合酶抑制剂的抗逆转录病毒药物方案（INI-CR）之间的相互作用，因为有证据表明，在免疫状态无关的情况下，在营养状况不佳的患者中启动 cART 是死亡率的预测因素。
将 120 只刚断奶的 Sprague Dawley 大鼠随机分为标准、LPHC 和正常蛋白高热量（NPHC）饮食组（每组 40 只），最初进行 15 周。此后，每组饮食组中的实验动物进一步随机分为四个治疗亚组（每组 10 只）：对照组（生理盐水）、第 1 组（TDF+3TC+DTG 和 Tesamorelin）、第 2 组（TDF+3TC+DTG）和阳性对照组（AZT+3TC+ATV/r），联合治疗和饮食治疗 9 周。在第 24 周评估每周体重、空腹血糖（FBG）、口服葡萄糖耐量试验（OGTT）；血脂谱、肝重、肝甘油三酯和肥胖程度。
在第 15 周，第 1 阶段（标准 146 ± 1.64 与 273.1 ± 1.56 g）、（NPHC，143.5 ± 2.40 与 390.2 ± 4.94 g）和（LPHC，145.5 ± 2.28 g 与 398.3 ± 4.89 g）之间的饮食组体重增加（p<0.0001）。FBG 和 OGTT 也有类似的增加（p<0.0001）。在第 2 阶段，NPHC 和 LPHC 饮食组的第 2 组和阳性对照组的 FBG、OGTT、体重、血脂谱、肝重、肝甘油三酯、肥胖和胰岛素水平均增加（p<0.0001）。Tesamorelin 无第 2 组和 NPHC 和 LPHC 阳性对照组的生长激素水平下降（p<0.0001）。
LPHC 饮食的致肥胖活性超过 NPHC 饮食，并与包含整合酶的和经典的 cART 药物方案相互作用，以重现与 cART 相关的代谢失调。然而，通过联合使用合成生长激素释放激素类似物 Tesamorelin，这些作用得到了逆转。
