Intermittent fasting promotes remodeling of neural and vascular networks in visceral white adipose tissue

ABSTRACT: Intermittent fasting (IF) improves metabolic health, in part by remodeling white adipose tissue (WAT), yet the underlying mechanisms remain elusive. Here, we show that IF induces coordinated neurovascular remodeling in visceral WAT, marked by increased angiogenesis and sympathetic innervation. Using tissue clearing and three-dimensional visualization, we show that a 16-week IF regimen increases vascular density and sympathetic nerve fiber branching in perigonadal WAT. Transcriptomic profiling reveals robust upregulation of neurotrophic and browning-associated genes, including neuregulin 4 (NRG4), which we identify as a key mediator of sympathetic neurite growth. Co-culture experiments with SH-SY5Y neuron-like cells and WAT explants suggest that IF-treated WAT promotes neurite branching via the NRG4-ErbB4 pathway. Inhibition of NRG4-ErbB4 pathway abrogates this effect, confirming its role in IF-induced sympathetic remodeling. Moreover, analysis of human visceral adipose tissue RNA-seq data shows a strong positive correlation between NRG4 expression and browning gene signatures. Together, these findings uncover a previously unappreciated role of IF in driving sympathetic remodeling of WAT via NRG4, offering mechanistic insights into its metabolic benefits and revealing a potential therapeutic target for obesity-related disorders.

INSTRUMENT(S): Isoflurane euthanasia chamber, Nugen Ovation SPIA; Wafergen’s Apollo liquid handler; KAPA Hyper Prep Library Kit, QIAGEN TissueLyser II, Illumina HiSeq 2000, Python

ORGANISM(S): Mus musculus

SUBMITTER: Annie Yew 

PROVIDER: E-MTAB-16066 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress