Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA.
Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA.
Am J Clin Nutr. 2023 Jan;117(1):121-129. doi: 10.1016/j.ajcnut.2022.10.001. Epub 2022 Dec 15.
MicroRNA 128-1 (miR-128-1) was recently linked to the evolutionary adaptation to famine and identified as a thrifty microRNA that controls energy expenditure, contributing to obesity and impaired glucose metabolism.
We investigated whether circulating miR-128-1-5p and its temporal changes in response to weight-loss diet interventions were related to regulating insulin resistance, adiposity, and energy expenditure in adults with overweight and obesity. We also examined whether habitual physical activity (PA) and different macronutrient intakes modified associations of changes in miR-128-1-5p with improved metabolic outcomes.
This study included 495 adults who consumed weight-loss diets with different macronutrient intakes. Circulating levels of miR-128-1-5p were assessed at baseline and 6 mo after the interventions. Outcome measurements included changes in insulin resistance HOMA-IR, adiposity, and resting energy expenditure.
We observed significant relations between circulating miR-128-1-5p and the positive selection signals at the 2q21.3 locus assessed by the single nucleotide polymorphisms rs1446585 and rs4988235. Higher miR-128-1-5p levels were associated with greater HOMA-IR (β per 1 SD: 0.08 [SE 0.03]; P = 0.009), waist circumference (β, 1.16 [0.55]; P = 0.036), whole-body total % fat mass (β, 0.75 [0.30]; P = 0.013), and REE (β, 23 [11]; P = 0.037). In addition, higher miR-128-1-5p level was related to lower total PA index (β, -0.23 [0.07]; P = 0.001) and interacted with PA (P < 0.05) on changes in HOMA-IR and adiposity. We found that greater increases in miR-128-1-5p levels after the interventions were associated with lesser improvements in HOMA-IR and adiposity in participants with no change/decreases in PA. Furthermore, we found that dietary fat (P = 0.027) and protein (P= 0.055) intakes modified relations between changes in miR-128-1-5p and REE.
Circulating thrifty miRNA was linked to regulating body fat, insulin resistance, and energy metabolism. Temporal changes in circulating miR-128-1-5p were associated with better weight-loss outcomes during the interventions; habitual PA and dietary macronutrient intake may modify such relations. This trial was registered at clinicaltrials.gov as NCT00072995.
微小 RNA 128-1（miR-128-1）最近与对饥荒的进化适应有关，并被鉴定为控制能量消耗的节俭微小 RNA，有助于肥胖和葡萄糖代谢受损。
我们研究了循环 miR-128-1-5p 及其对减肥饮食干预的反应中的时间变化是否与调节超重和肥胖成年人的胰岛素抵抗、肥胖和能量消耗有关。我们还研究了习惯性体力活动（PA）和不同宏量营养素摄入量是否改变了 miR-128-1-5p 变化与改善代谢结果之间的关联。
这项研究包括 495 名成年人，他们食用了不同宏量营养素摄入量的减肥饮食。在干预前和 6 个月后评估循环 miR-128-1-5p 水平。结果测量包括胰岛素抵抗 HOMA-IR、肥胖和静息能量消耗的变化。
我们观察到循环 miR-128-1-5p 与通过单核苷酸多态性 rs1446585 和 rs4988235 评估的 2q21.3 位点的正选择信号之间存在显著关系。miR-128-1-5p 水平升高与 HOMA-IR 增加（每 1 SD 的 β：0.08 [SE 0.03]；P = 0.009）、腰围增加（β，1.16 [0.55]；P = 0.036）、全身总%脂肪量增加（β，0.75 [0.30]；P = 0.013）和 REE 增加（β，23 [11]；P = 0.037）有关。此外，miR-128-1-5p 水平升高与总 PA 指数降低（β，-0.23 [0.07]；P = 0.001）有关，并且与 PA 相互作用（P < 0.05）有关，影响 HOMA-IR 和肥胖的变化。我们发现，干预后 miR-128-1-5p 水平的升高与 PA 无变化/减少的参与者中 HOMA-IR 和肥胖的改善程度较低有关。此外，我们发现膳食脂肪（P = 0.027）和蛋白质（P = 0.055）摄入量改变了 miR-128-1-5p 变化与 REE 之间的关系。
循环节俭 miRNA 与调节体脂肪、胰岛素抵抗和能量代谢有关。循环 miR-128-1-5p 的时间变化与干预期间更好的减肥效果有关；习惯性 PA 和膳食宏量营养素摄入可能会改变这种关系。该试验在 clinicaltrials.gov 上注册为 NCT00072995。
