Abstract

(1) Background: White adipose tissue (WAT) is a dynamic and plastic tissue showing high sensitivity to carbohydrate supply. In such a context, the WAT may accordingly modulate its mitochondrial metabolic activity. We previously demonstrated that a partial replacement of glucose by galactose in a culture medium of 3T3-L1 cells leads to a poorer adipogenic yield and improved global mitochondrial health. In the present study, we investigate key mitochondrial metabolic actors reflecting mitochondrial adaptation in response to different carbohydrate supplies. (2) Methods: The metabolome of 3T3-L1 cells was investigated during the differentiation process using different glucose/galactose ratios and by a targeted approach using 1H-NMR (Proton nuclear magnetic resonance) spectroscopy; (3) Results: Our findings indicate a reduction of adipogenic and metabolic overload markers under the low glucose/galactose condition. In addition, a remodeling of the mitochondrial function triggers the secretion of metabolites with signaling and systemic energetical homeostasis functions. Finally, this study also sheds light on a new way to consider the mitochondrial metabolic function by considering noncarbohydrates related pathways reflecting both healthier cellular and mitochondrial adaptation mechanisms; (4) Conclusions: Different carbohydrates supplies induce deep mitochondrial metabolic and function adaptations leading to overall adipocytes function and profile remodeling during the adipogenesis.

Highlights

  • We previously reported that the partial replacement of glucose by galactose in the culture medium of 3T3-L1 cells had an anti-adipogenic effect and globally improved their mitochondrial health [18]

  • In the white adipose tissue (WAT), the other pathways using galactose as a substrate were not detected and are represented by a dotted arrow ending by a question mark

  • This study aiming at a deeper investigation of the anti-adipogenic and mitochondrial metabolic function modulation in LG-GAL condition gave rise to new considerations about the metabolism assessment thanks to a targeted 1 H-NMR-based metabolomics approach used

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Summary

Introduction

It is accepted that WAT dynamics are challenged by several environmental features in both physiological and pathological contexts, such as obesity and metabolic disorders. Those adaptations lead to cellular changes known as WAT remodeling, including processes leading to the expansion of the tissue storage capacity by inducing an increase of adipocytes number. In this context, adipogenesis, the mechanism through which precursors cells differentiate into mature and functional adipocytes, has been extensively studied [1,2].

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