Dataset Information

Role of Liver Fatty Acid-Binding Protein (LFABP) in Adipose Tissue Metabolism

ABSTRACT: Obesity and adipose tissues quality are important risk factors for the development of type 2 diabetes and metabolic syndrome; this risk is related to intrinsic differences in the behavior of adipocytes in different fat depots. We have shown that the liver fatty acid-binding protein null (LFABP-/-) mouse is a model of the ‘metabolically healthy obese’ (MHO) state. Here, we demonstrate that the LFABP-/- mouse is a novel model of hyperplastic subcutaneous adipose tissue (SAT). LFABP-/-mice fed a high-fat diet (HFD) for 12 weeks gained 27% more weight (BW, g: 43.6 LFABP-/- vs 34.4 WT, P<0.001, n=10) and their fat mass was almost double (Fat, g: 15.4 LFABP-/-vs8.3 WT, P<0.001, n=10) that of WT. Intriguingly, despite the substantial increase in mass, inguinal white adipose tissue (iWAT) adipocyte size was >4-fold smaller (46pL LFABP-/-vs222pL WT per cell, P<0.001, n=5) and adipocyte number was 5-fold higher (23.6 LFABP-/-vs4.7 WT x 106, P=0.001, n=5) in the iWAT of LFABP-/-compared to WT mice. Upon obesity development, Lfabp deletion results in transcriptomic differences that include large effects on cholesterol biosynthesis and extracellular matrix (ECM) remodeling, likely leading to tissue growth and a state of ‘adaptive fibrosis’ and ‘homeostatic adipogenesis’ for safe excess energy storage. Since LFABP is not expressed in adipose tissues, these results suggest that its ablation promotes interorgan signaling that may limit hypertrophy and drive hyperplasia in expansion of potentially metabolically beneficial SAT, contributing to the MHO phenotype of the LFABP-/-mouse.

ORGANISM(S): Mus musculus

PROVIDER: GSE277001 | GEO | 2025/06/18

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Background/aims: Serum concentrations of the hepatokine fibroblast growth factor (FGF) 21 are elevated in obesity, type‐2 diabetes, and the metabolic syndrome. We asked whether FGF21 levels differ between subjects with metabolically healthy vs. unhealthy obesity (MHO vs. MUHO) opening the possibility that FGF21 is a cross‐talker between liver and adipose tissue in MUHO. Furthermore, we studied the effects of chronic FGF21 treatment on adipocyte differentiation, lipid storage, and adipokine secretion. Methods/study design: In 20 morbidly obese donors of abdominal subcutaneous fat biopsies discordant for their whole‐body insulin sensitivity (hereby classified as MHO or MUHO subjects), serum FGF21 was quantified. The impact of chronic FGF21 treatment on differentiation, lipid accumulation, and adipokine release was assessed in isolated preadipocytes differentiated in vitro. Results: Serum FGF21 concentrations were more than two‐fold higher in MUHO as compared to 37 MHO subjects (457 ±378 vs. 211 ±123 pg/mL; p<0.05). FGF21 treatment of human preadipocytes for the entire differentiation period was modestly lipogenic (+15%; p<0.05), reduced the expression of key adipogenic transcription factors (PPARG and CEBPA, ‐15% and ‐40%, respectively; p<0.01 both), reduced adiponectin expression (‐20%; p<0.05), markedly reduced adiponectin release (‐60%; p<0.01), and substantially increased leptin (+60%; p<0.01) and interleukin‐6 (+50%; p<0.001) release. Interpretation/conclusions: The hepatokine FGF21 exerts weak lipogenic and anti‐adipogenic actions and marked adiponectin‐suppressive and leptin and interleukin‐6 release‐promoting effects in human differentiating preadipocytes. Together with the higher serum concentrations in MUHO subjects, our findings reveal FGF21 as a circulating factor promoting the development of metabolically unhealthy adipocytes. We analysed in vitro differentiated preadipocytes from 20 human donors treated with FGF21 or control cultures.

Dataset Information

Role of Liver Fatty Acid-Binding Protein (LFABP) in Adipose Tissue Metabolism

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets