高脂饮食中添加补充黄连素可减少患有妊娠期糖尿病的母鼠后代的肥胖和心脏功能障碍。

Supplemental Berberine in a High-Fat Diet Reduces Adiposity and Cardiac Dysfunction in Offspring of Mouse Dams with Gestational Diabetes Mellitus.

机构信息

Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Theme, Children's Hospital Research Institute of Manitoba, Department of Pharmacology and Therapeutics, Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.

Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun, China.

出版信息

J Nutr. 2021 Apr 8;151(4):892-901. doi: 10.1093/jn/nxaa408.

DOI:10.1093/jn/nxaa408

PMID:33484149

Abstract

BACKGROUND

There are few evidence-based strategies to attenuate the risk of metabolic syndrome in offspring exposed to gestational diabetes mellitus (GDM). Berberine (BBR) is an isoquinoline alkaloid extracted from Chinese herbs and exhibits glucose lowering properties.

OBJECTIVES

We hypothesized that dietary BBR would improve health outcomes in the mouse offspring of GDM dams.

METHODS

Wild-type C57BL/6 female mice were fed either a Lean-inducing low-fat diet (L-LF,10% kcal fat, 35% kcal sucrose) or a GDM-inducing high-fat diet (GDM-HF, 45% kcal fat, 17.5% sucrose) for 6 wk prior to breeding with wild-type C57BL/6 male mice throughout pregnancy and the suckling period. The resulting Lean and GDM-exposed male and female offspring were randomly assigned an LF (10% kcal fat, 35% kcal sucrose), HF (45% kcal fat, 17.5% sucrose), or high-fat berberine (HFB) (45% kcal fat, 17.5% sucrose diet) containing BBR (160 mg/kg/d, HFB) at weaning for 12 wk. The main outcome was to evaluate the effects of BBR on obesity, pancreatic islet function, and cardiac contractility in GDM-exposed HF-fed offspring. Significance between measurements was determined using a 2 (gestational exposure) × 3 (diet) factorial design by a 2- way ANOVA using Tukey post-hoc analysis.

RESULTS

In the GDM-HF group, body weights were significantly increased (16%) compared with those in baseline (L-LF) animals (P < 0.05). Compared with the L-LF animals, the GDM-HF group had a reduction in pancreatic insulin glucose-stimulated insulin secretion (74%) and increased cardiac isovolumetric contraction time (IVCT; ∼150%) (P < 0.05). Compared with GDM-HF animals, the GDM-HFB group with the dietary addition of BBR had significantly reduced body weight (16%), increased glucose-stimulated insulin secretion from pancreatic islets (254%), and reduced systolic heart function (46% IVCT) (P < 0.05).

CONCLUSIONS

In a mouse model of GDM, dietary BBR treatment provided protection from obesity and the development of pancreatic islet and cardiac dysfunction.

摘要

背景

在暴露于妊娠糖尿病（GDM）的后代中，减轻代谢综合征风险的循证策略很少。小檗碱（BBR）是一种从中药中提取的异喹啉生物碱，具有降血糖作用。

目的

我们假设饮食 BBR 会改善 GDM 母鼠后代的健康结果。

方法

将野生型 C57BL/6 雌性小鼠分别用诱导低脂饮食（L-LF，10%卡路里脂肪，35%卡路里蔗糖）或诱导高脂肪饮食（GDM-HF，45%卡路里脂肪，17.5%蔗糖）喂养 6 周，然后与野生型 C57BL/6 雄性小鼠交配，并在妊娠和哺乳期全程用高脂肪饮食喂养。由此产生的瘦鼠和 GDM 暴露的雄性和雌性后代在断奶时被随机分配到 LF（10%卡路里脂肪，35%卡路里蔗糖）、HF（45%卡路里脂肪，17.5%蔗糖）或含有 BBR（160mg/kg/d，HFB）的高脂肪小檗碱（HFB）饮食中 12 周。主要结果是评估 BBR 对 GDM 暴露的 HF 喂养后代肥胖、胰岛功能和心脏收缩力的影响。使用双因素方差分析（两因素为妊娠暴露，三因素为饮食），通过 Tukey 事后分析确定测量值之间的差异。

结果

与基线（L-LF）动物相比，GDM-HF 组的体重显著增加（16%）（P<0.05）。与 L-LF 动物相比，GDM-HF 组胰岛胰岛素葡萄糖刺激胰岛素分泌减少（74%），心等容收缩时间（IVCT）增加（约 150%）（P<0.05）。与 GDM-HF 动物相比，添加 BBR 的 GDM-HFB 组体重显著降低（16%），胰岛葡萄糖刺激胰岛素分泌增加（254%），收缩期心脏功能降低（46%IVCT）（P<0.05）。