Maternal dietary fat during lactation shapes single nucleus transcriptomic profile of postnatal offspring hypothalamus in a sexually dimorphic manner in mice.
Yi HuangAnyongqi WangWenjiang ZhouBaoguo LiLinshan ZhangAgata M RudolfZengguang JinCatherine HamblyGuanlin WangJohn R SpeakmanPublished in: Nature communications (2024)
Maternal overnutrition during lactation predisposes offspring to develop metabolic diseases and exacerbates the relevant syndromes in males more than females in later life. The hypothalamus is a heterogenous brain region that regulates energy balance. Here we combined metabolic trait quantification of mother and offspring mice under low and high fat diet (HFD) feeding during lactation, with single nucleus transcriptomic profiling of their offspring hypothalamus at peak lacation to understand the cellular and molecular alterations in response to maternal dietary pertubation. We found significant expansion in neuronal subpopulations including histaminergic (Hdc), arginine vasopressin/retinoic acid receptor-related orphan receptor β (Avp/Rorb) and agouti-related peptide/neuropeptide Y (AgRP/Npy) in male offspring when their mothers were fed HFD, and increased Npy-astrocyte interactions in offspring responding to maternal overnutrition. Our study provides a comprehensive offspring hypothalamus map at the peak lactation and reveals how the cellular subpopulations respond to maternal dietary fat in a sex-specific manner during development.
Keyphrases
- high fat diet
- adipose tissue
- insulin resistance
- birth weight
- human milk
- dairy cows
- pregnancy outcomes
- high fat diet induced
- single cell
- nitric oxide
- preterm infants
- pregnant women
- body mass index
- rna seq
- skeletal muscle
- type diabetes
- dna methylation
- multiple sclerosis
- weight gain
- physical activity
- genome wide
- gestational age
- low birth weight
- functional connectivity
- white matter
- drug induced
- blood brain barrier
- single molecule