Nutrition Alters the Stiffness of Adipose Tissue and Cell Signaling

Abstract

Adipose tissue is a complex organ composed of various cell types and an extracellular matrix (ECM). The visceral adipose tissue (VAT) is dynamically altered in response to nutritional regimens that lead to local cues affecting the cells and ECM. The adipocytes are in conjunction with the surrounding ECM that maintains the tissue’s niche, provides a scaffold for cells and modulates their signaling. In this study, we provide a better understanding of the crosstalk between nutritional regimens and the ECM’s stiffness. Histological analyses showed that the adipocytes in mice fed a high-fat diet (HFD) were increased in size, while the ECM was also altered with changes in mass and composition. HFD-fed mice exhibited a decrease in elastin and an increase in collagenous proteins. Rheometer measurements revealed a stiffer ECM in whole tissue (nECM) and decellularized (deECM) in HFD-fed animals. These alterations in the ECM regulate cellular activity and influence their metabolic function. HFD-fed mice expressed high levels of the receptor for advanced-glycation-end-products (RAGE), indicating that AGEs might play a role in these processes. The cells also exhibited an increase in phosphoserine332 of IRS-1, a decrease in the GLUT4 transporter levels at the cells’ membrane, and a consequent reduction in insulin sensitivity. These results show how alterations in the stiffness of ECM proteins can affect the mechanical cues transferred to adipocytes and, thereby, influence the adipocytes’ functionality, leading to metabolic disorders.

Improved whole-mount immunofluorescence protocol for consistent and robust labeling of adultDrosophila melanogasteradipose tissue

“…The protocol described here, in conjunction with fluorescence microscopy, can be used to examine adipose tissue cellular biology during homeostasis as well as in response to genetic manipulations and/or changes in organismal physiology. In mammals, age, diet, sex, exercise, and hormones influence fat body distribution, adipocyte proliferation, differentiation, and growth, adipose tissue browning and beiging, lipid storage, metabolic activity, and gene expression (Boulet et al, 2022; Farris et al, 2024; Lu et al, 2023; Naftaly et al, 2022; Pérez et al, 2016; Stanford and Goodyear, 2016; Zhao and Yue, 2024). Similarly, Drosophila fat body cellular morphology, mass, molecular signature, as well as energy storage and endocrine roles respond to aging, dietary input, physical activity, and sexual dimorphism (Diaz et al, 2023; Huang et al, 2022; Lu et al, 2023; Matsuoka et al, 2017; Song et al, 2023; Wat et al, 2020; Wat et al, 2021).…”

Advance Glycation End-products accelerate amyloid deposits in adipocyte’s lipid droplets

“…Epididymal white visceral adipose tissue (WAT) were collected from C57BL/6J mice (Envigo RMS Limited, Jerusalem, Israel) and immediately used as fresh, frozen (by liquid nitrogen) or for mature adipocyte isolation following collagenase digestion as previously described (56, 57). The mice were kept in a conventional facility of Tel Aviv University (TAU) with 12 h light/dark cycles and were fed with standard chow diet and water were provided ad libitum.…”

“…Visceral adipose tissues (VAT) -Epididymal white visceral adipose tissue (WAT) were collected from C57BL/6J mice (Envigo RMS Limited, Jerusalem, Israel) and immediately used as fresh, frozen (by liquid nitrogen) or for mature adipocyte isolation following collagenase digestion as previously described (56,57).…”

(Patho)Physiology of Glycosylphosphatidylinositol-Anchored Proteins II: Intercellular Transfer of Matter (Inheritance?) That Matters

“…The main conclusions are as follows (numbering of the distinct steps as shown in Supplementary Materials, Figure S1): Full-length GPI-APs are released from the outer leaflet of the PM bilayer of large lipid-loaded human adipocytes (panel b, upper compartment, "direct" transfer) into the interstitial spaces of adipose tissue depots (1). Specific characteristics of the adipocyte PMs (e.g., viscoelasticity, stiffness), which have been found to be correlated to the age and metabolic state of both rat and human adipocytes [137][138][139][140], may support release. Released GPI-APs are inserted into the outer leaflet of the PM bilayer of small (pre)adipocytes, which contain only small lipid droplets and few GPI-APs and reside near to the large adipocytes within the same tissue depot (2).…”