Adipocyte-hepatocyte crosstalk in cellular models of obesity: Role of soluble factors

Baldini, Francesca; Diab, Farah; Serale, Nadia; Zeaiter, Lama; Portincasa, Piero; Diaspro, Alberto; Vergani, Laura

doi:10.1016/j.lfs.2023.121464

Cited by 3 publications

(2 citation statements)

References 41 publications

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“…An increase of adipocyte size is associated with a deregulation in metabolic-related hormone secretion [ 12 ]. In our results, MexMix significantly restored the secretion of MASLD development-related adipokines.…”

Section: Resultsmentioning

confidence: 99%

A Novel Foodstuff Mixture Improves the Gut–Liver Axis in MASLD Mice and the Gut Microbiota in Overweight/Obese Patients

Rosas-Campos,

Sandoval-Rodríguez,

Rodríguez-Sanabria

et al. 2024

Antioxidants

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Microbial community control is crucial for maintaining homeostasis of the gut–liver axis in metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we show that supplementation with a mixture of Mexican foodstuffs (MexMix)—Opuntia ficus indica (nopal), Theobroma cacao (cocoa) and Acheta domesticus (crickets)—enriches several beneficial taxa in MASLD mice and overweight/obese humans. Thus, MexMix induces an important prebiotic effect. In mice, a restoration of intestinal health was observed due to the increased short-chain fatty acids (SCFAs) and intestinal crypt depth, Ocln and Cldn1 expression, and decreased Il6 and Tnfa expression. MexMix significantly reduced steatosis in the mice’s liver and modified the expression of 1668 genes. By PCR, we corroborated a Tnfa and Pparg decrease, and a Cat and Sod increase. In addition, MexMix increased the hepatic NRF2 nuclear translocation and miRNA-34a, miRNA-103, and miRNA-33 decline. In overweight/obese humans, MexMix improved the body image satisfaction and reduced the fat intake. These findings indicate that this new food formulation has potential as a therapeutic approach to treat conditions associated with excessive consumption of fats and sugars.

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Section: Resultsmentioning

confidence: 99%

A Novel Foodstuff Mixture Improves the Gut–Liver Axis in MASLD Mice and the Gut Microbiota in Overweight/Obese Patients

Rosas-Campos,

Sandoval-Rodríguez,

Rodríguez-Sanabria

et al. 2024

Antioxidants

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“…To induce adipogenic differentiation, confluent pre-adipocytes cultured in DMEM medium were exposed to adipogenic mixture consisting of 1.7 μM insulin, 1 μM dexamethasone (DEXA), and 500 μM 3-isobutyl-1-methylxanthine (IBMX) for 48 hours [ 25 ]. Subsequently, the medium was replaced with fresh medium containing 1.7 μM insulin, and medium changes were performed every 48 hours for a total of 6 days [ 26 , 27 ]. On the 7th day, the cells were harvested for microscopy acquisition and seeded on collagenated glass coverslides.…”

Section: Methodsmentioning

confidence: 99%

Unveiling nuclear chromatin distribution using IsoConcentraChromJ: A flourescence imaging plugin for IsoRegional and IsoVolumetric based ratios analysis

Zeaiter,

Dabbous,

Baldini

et al. 2024

PLoS ONE

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Chromatin exhibits non-random distribution within the nucleus being arranged into discrete domains that are spatially organized throughout the nuclear space. Both the spatial distribution and structural rearrangement of chromatin domains in the nucleus depend on epigenetic modifications of DNA and/or histones and structural elements such as the nuclear envelope. These components collectively contribute to the organization and rearrangement of chromatin domains, thereby influencing genome architecture and functional regulation. This study develops an innovative, user-friendly, ImageJ-based plugin, called IsoConcentraChromJ, aimed quantitatively delineating the spatial distribution of chromatin regions in concentric patterns. The IsoConcentraChromJ can be applied to quantitative chromatin analysis in both two- and three-dimensional spaces. After DNA and histone staining with fluorescent probes, high-resolution images of nuclei have been obtained using advanced fluorescence microscopy approaches, including confocal and stimulated emission depletion (STED) microscopy. IsoConcentraChromJ workflow comprises the following sequential steps: nucleus segmentation, thresholding, masking, normalization, and trisection with specified ratios for either 2D or 3D acquisitions. The effectiveness of the IsoConcentraChromJ has been validated and demonstrated using experimental datasets consisting in nuclei images of pre-adipocytes and mature adipocytes, encompassing both 2D and 3D imaging. The outcomes allow to characterize the nuclear architecture by calculating the ratios between specific concentric nuclear areas/volumes of acetylated chromatin with respect to total acetylated chromatin and/or total DNA. The novel IsoConcentrapChromJ plugin could represent a valuable resource for researchers investigating the rearrangement of chromatin architecture driven by epigenetic mechanisms using nuclear images obtained by different fluorescence microscopy methods.

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Adipocyte inflammation is the primary driver of hepatic insulin resistance in a human iPSC-based microphysiological system

Qi,

Groeger,

Sharma

et al. 2024

Nat Commun

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Interactions between adipose tissue, liver and immune system are at the center of metabolic dysfunction-associated steatotic liver disease and type 2 diabetes. To address the need for an accurate in vitro model, we establish an interconnected microphysiological system (MPS) containing white adipocytes, hepatocytes and proinflammatory macrophages derived from isogenic human induced pluripotent stem cells. Using this MPS, we find that increasing the adipocyte-to-hepatocyte ratio moderately affects hepatocyte function, whereas macrophage-induced adipocyte inflammation causes lipid accumulation in hepatocytes and MPS-wide insulin resistance, corresponding to initiation of metabolic dysfunction-associated steatotic liver disease. We also use our MPS to identify and characterize pharmacological intervention strategies for hepatic steatosis and systemic insulin resistance and find that the glucagon-like peptide-1 receptor agonist semaglutide improves hepatocyte function by acting specifically on adipocytes. These results establish our MPS modeling the adipose tissue-liver axis as an alternative to animal models for mechanistic studies or drug discovery in metabolic diseases.

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Adipocyte-hepatocyte crosstalk in cellular models of obesity: Role of soluble factors

Cited by 3 publications

References 41 publications

A Novel Foodstuff Mixture Improves the Gut–Liver Axis in MASLD Mice and the Gut Microbiota in Overweight/Obese Patients

A Novel Foodstuff Mixture Improves the Gut–Liver Axis in MASLD Mice and the Gut Microbiota in Overweight/Obese Patients

Unveiling nuclear chromatin distribution using IsoConcentraChromJ: A flourescence imaging plugin for IsoRegional and IsoVolumetric based ratios analysis

Adipocyte inflammation is the primary driver of hepatic insulin resistance in a human iPSC-based microphysiological system

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