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Encapsulation Thermogenic Preadipocytes for Transplantation into Adipose Tissue Depots

Cell encapsulation was developed to entrap viable cells within semi-permeable membranes. The engrafted encapsulated cells can exchange low molecular ...

The Ohio State University

Zinc (Zn) deficiency and obesity are global public health problems. Zn deficiency is associated with obesity and comorbid conditions that include insulin resistance and type 2 diabetes. However, the function of Zn in obesity remains unclear. Using a mouse model of combined high-fat and low-Zn intake (0.5-1.5 mg/kg), we investigated whether Zn deficiency exacerbates the extent of adiposity as well as perturbations in metabolic and immune function. C57BL/6 mice were randomly assigned to receive either a high-fat diet (HFD) or a control (C) diet for 6 wk, followed by further subdivision into 2 additional groups fed Zn-deficient diets (C-Zn, HFD-Zn), along with a C diet and an HFD, for 3 wk (n = 8-9 mice/group). The extent of visceral fat, insulin resistance, or systemic inflammation was unaffected by Zn deficiency. Strikingly, Zn deficiency significantly augmented circulating leptin concentrations (HFD-Zn vs. HFD: 3.15 ± 0.16 vs. 2.59 ± 0.12 μg/L, respectively) and leptin signaling in the liver of obese mice. Furthermore, gene expression of macrophage-specific markers ADAM8 (A disintegrin and metalloproteinase domain-containing protein 8) and CD68 (cluster of differentiation 68) was significantly greater in adipose tissue in the HFD-Zn group than in the HFD group, as confirmed by CD68 protein analysis, indicative of increased macrophage infiltration. Inspection of Zn content and mRNA profiles of all Zn transporters in the adipose tissue revealed alterations of Zn metabolism to obesity and Zn deficiency. Our results demonstrate that Zn deficiency increases leptin production and exacerbates macrophage infiltration into adipose tissue in obese mice, indicating the importance of Zn in metabolic and immune dysregulation in obesity.

Zinc deficiency augments leptin production and exacerbates macrophage infiltration into adipose tissue in mice fed a high-fat diet.

Three fluorescence biosensors were developed based on a 3T3-L1 preadipocyte line that stably expressed Nfkb-RE/GFP, Fabp4-P/CFP, and Nrf2-P/YFP fluorescent reporters. We hypothesized that nutraceuticals' inflammatory, adipogenic, and antioxidant status will be identified based on the change in fluorescence in reporter adipocytes. We validated these assays with activators of NFκB, FABP4-regulating peroxisome proliferator activated receptor gamma, NFR2 and, thereafter, tested known and unknown properties of mangostines (MGs), the xanthone metabolites in mangosteen fruit.

Adipocyte reporter assays: application for identification of anti-inflammatory and antioxidant properties of mangosteen xanthones.

How composition of egg yolk (EY) influences NF-κB, a key transcription pathway in inflammation, remains unclear. We performed partial delipidation of EY that removed 20-30% of cholesterol and triglycerides. The resulting polar and nonpolar fractions were termed EY-P and EY-NP. NF-κB activation in response to EY from different suppliers and their fractions was examined in 3T3-L1 adipocytes using a NF-κB response element reporter assay and by analyzing expression of 248 inflammatory genes. Although EY-P and EY contained similar level of vitamins, carotenoids, and fatty acids, only delipidated EY-P fraction suppressed NF-κB via down-regulation of toll like receptor-2 and up-regulation of inhibitory toll interacting protein (Tollip) and lymphocyte antigen 96 (Ly96). Our data suggest that anti-inflammatory activity of lutein and retinol were blunted by nonpolar lipids in EY, likely via crosstalk between SREBP and NF-κB pathways in adipocytes. Thus, moderate delipidation may improve the beneficial properties of regular eggs.

Qiwen Shen

Department of Human Sciences

The Ohio State University

Encapsulation Thermogenic Preadipocytes for Transplantation into Adipose Tissue Depots

Qiwen Shen

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Human Sciences

The Ohio State University

Encapsulation Thermogenic Preadipocytes for Transplantation into Adipose Tissue Depots

Department of Human Sciences