Scholarlink

Background <p>Adipokines regulate body weight and metabolism by targeting the hypothalamus, influencing feeding, energy expenditure (EE) and insulin sensitivity. Angiopoietin-like 2 (Angptl2) is a pro-inflammatory adipokine linking obesity to insulin resistance. Both Angptl2 and its receptor are expressed in the central nervous system. Yet, the contribution of Angptl2 to the regulation of energy metabolism and relevant hypothalamic neuropeptides in male and female mice is unknown. We aim at determining the impact of <i>Angptl2</i> knockdown (KD) on energy balance, nutrient partitioning and hypothalamic responses to a standard (STD) or high-fat diet (HFD) in mice.</p> Methods <p>Three-month-old male and female <i>Angptl2</i>-KD mice and wildtype (WT) littermates were fed 16 weeks either a STD or a HFD. Body weight, food consumption and insulin sensitivity were assessed along with measurements of EE, respiratory exchange ratio (RER) and locomotor activity. We quantified the expression of <i>Angptl2</i> and its receptors <i>itga5, mag</i> and <i>pirb</i> in the medio-basal hypothalamus (MBH) of WT mice, and MBH neuropeptide Y (<i>NPY</i>), agouti-related neuropeptide (<i>AgRP</i>) and proopiomelanocortin (<i>POMC</i>) gene expression in both KD and control fasting mice.</p> Results <p>Lack of <i>Angptl2</i> reduced food intake in males on both diets, and in females on HFD. In KD males, this anorexigenic effect was associated with lower body weight, increased EE, improved insulin sensitivity and lower hypothalamic orexigenic <i>NPY</i> expression compared to controls. Female <i>Angptl2</i>-KD mice however, exhibited unaltered body weight, EE and insulin sensitivity, and elevated <i>NPY</i>, <i>AgRP</i> and <i>MC4R</i> expression compared to controls. Fasting caused an increase in the MBH of <i>mag</i> expression in males and females but <i>Angptl2</i> expression only in female mice.</p> Conclusions <p><i>Angptl2</i> KD improved diet-induced obesity and associated metabolic dysfunction in male mice. The lack of similar changes in female mice and divergent MBH neuropeptide profile suggest that sex-dependent mechanisms underly the anabolic effects of this proinflammatory adipokine.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Sexually dimorphic effects of angiopoietin-like 2 on energy metabolism and hypothalamic neuropeptide regulation

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年3月26日

查看全文
  • Romane Manceau,
  • Pinçon Anthony,
  • Cécile Hryhorczuk,
  • Pauline Labbé,
  • Nathalie Thorin-Trescases,
  • Stephanie Fulton,
  • Éric Thorin

摘要

Background

Adipokines regulate body weight and metabolism by targeting the hypothalamus, influencing feeding, energy expenditure (EE) and insulin sensitivity. Angiopoietin-like 2 (Angptl2) is a pro-inflammatory adipokine linking obesity to insulin resistance. Both Angptl2 and its receptor are expressed in the central nervous system. Yet, the contribution of Angptl2 to the regulation of energy metabolism and relevant hypothalamic neuropeptides in male and female mice is unknown. We aim at determining the impact of Angptl2 knockdown (KD) on energy balance, nutrient partitioning and hypothalamic responses to a standard (STD) or high-fat diet (HFD) in mice.

Methods

Three-month-old male and female Angptl2-KD mice and wildtype (WT) littermates were fed 16 weeks either a STD or a HFD. Body weight, food consumption and insulin sensitivity were assessed along with measurements of EE, respiratory exchange ratio (RER) and locomotor activity. We quantified the expression of Angptl2 and its receptors itga5, mag and pirb in the medio-basal hypothalamus (MBH) of WT mice, and MBH neuropeptide Y (NPY), agouti-related neuropeptide (AgRP) and proopiomelanocortin (POMC) gene expression in both KD and control fasting mice.

Results

Lack of Angptl2 reduced food intake in males on both diets, and in females on HFD. In KD males, this anorexigenic effect was associated with lower body weight, increased EE, improved insulin sensitivity and lower hypothalamic orexigenic NPY expression compared to controls. Female Angptl2-KD mice however, exhibited unaltered body weight, EE and insulin sensitivity, and elevated NPY, AgRP and MC4R expression compared to controls. Fasting caused an increase in the MBH of mag expression in males and females but Angptl2 expression only in female mice.

Conclusions

Angptl2 KD improved diet-induced obesity and associated metabolic dysfunction in male mice. The lack of similar changes in female mice and divergent MBH neuropeptide profile suggest that sex-dependent mechanisms underly the anabolic effects of this proinflammatory adipokine.