Aging Impairs Cold-Induced Beige Adipogenesis and Adipocyte Metabolic Reprogramming

Core Concepts

Aging inhibits beige adipogenesis and metabolic reprogramming in response to cold exposure.

Abstract

This study explores the impact of aging on beige adipose tissue development, focusing on ASPCs and adipocytes during the beiging process. Aging increases fibro-inflammatory gene expression in ASPCs, blocking their differentiation into beige adipocytes. Single nucleus RNA-sequencing reveals compositional and transcriptional differences in adipocyte populations with age and cold exposure. Cold exposure induces a population of adipocytes expressing high levels of de novo lipogenesis genes, which is reduced in aged animals. Npr3, a beige fat repressor, is identified as an aging-upregulated gene in white adipocytes.
Abstract:

Beige adipose tissue has therapeutic potential for obesity.
Aging impacts ASPCs and adipocytes during beiging.
Fibroblastic ASPCs show altered gene expression with age.
Cold exposure induces distinct responses in young vs. aged mice.
Introduction:

Brown and beige fat cells burn calories for heat production.
Beige fat development reduces obesity and improves health.
Aging leads to a decline in thermogenic activity.
Various processes contribute to the aging-induced deficit in beige fat formation.
Results:

Aged mice exhibit decreased iWAT beiging in response to cold exposure.
Beige adipose tissue induction is impaired in middle-aged mice.
Aging blocks beige adipogenesis from Pdgfra+ ASPCs.
Single-cell profiling reveals distinct responses to cold exposure and aging.
Discussion:

Aging impairs beige fat formation through non-cell-autonomous effects.
Gene expression analysis identifies markers dysregulated by aging.
DNL-high cells show dramatic changes during cold exposure.

Stats

Aging or cold exposure did not induce dramatic shifts in either the proportions or gene expression signatures of any of these ASPC types, suggesting that these cell populations are stably maintained across a range of conditions.

Quotes

"Aging blocks beige adipogenesis from fibroblastic ASPCs."
"Expression profiling at the single-cell level reveals adipocyte heterogeneity."

Key Insights Distilled From

Aging impairs cold-induced beige adipogenesis and adipocyte metabolic reprogramming

by Holman,C. D.... at www.biorxiv.org 03-23-2023

https://www.biorxiv.org/content/10.1101/2023.03.20.533514v2

Deeper Inquiries

How do environmental factors suppress adipogenesis?

Environmental factors can suppress adipogenesis through various mechanisms. In the context of the study provided, aging was shown to block beige adipogenesis by affecting the profile and activity of adipocyte stem and progenitor cells (ASPCs). Aging increased the expression of fibro-inflammatory genes in ASPCs, such as Cd9, which are associated with fibrogenic processes. This upregulation of certain genes in ASPCs led to a blockage in their differentiation into beige adipocytes. Additionally, aging-induced changes in the tissue microenvironment may contribute to this suppression by altering signaling pathways that regulate adipogenesis.

What role does natriuretic peptide signaling play in aging-related impairment?

Natriuretic peptide signaling plays a significant role in aging-related impairment of beige fat development. Natriuretic peptides are known for their lipolytic and thermogenic effects on adipose tissue. The clearance receptor for natriuretic peptides, Npr3, acts as a negative regulator of these beneficial effects by reducing NP signaling. In aged animals, there is an upregulation of Npr3 expression levels within white adipocytes and DNL-high cells. This elevated expression inhibits the thermogenic gene program activation necessary for beige fat formation during cold exposure.

How can targeting natriuretic peptide signaling unlock beige fat development?

Targeting natriuretic peptide signaling presents a promising approach to unlocking beige fat development and overcoming age-related impairments in thermogenic capacity. By modulating Npr3 activity or expression levels within white adipocytes or other relevant cell populations, it may be possible to enhance NP signaling and promote thermogenesis within brown and beige fat depots. This targeted intervention could potentially restore the balance between lipid storage and utilization pathways required for efficient energy expenditure through heat production in response to cold exposure or other stimuli that induce beiging processes.