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Light-triggered methylcellulose gold nanoparticle hydrogels for leptin release to inhibit fat stores in adipocytes.

ABSTRACT: Leptin is released in response to increased triglyceride storage in adipocytes and impacts body weight, but has drawbacks such as poor therapeutic effect and side effects when delivered systemically. Leptin also modifies adipocyte sensitivity to insulin to inhibit lipid accumulation. Here, light-triggered degradation of hydrogels was used to improve accuracy and effectiveness for sustained and controllable release. In our approach, leptin was entrapped within methylcellulose (MC)-based hydrogels, with incorporation of gold nanoparticles (NP). The incorporation of gold NP into MC hydrogels led to a tunable light irradiation response that dictated the hydrogel release rate of leptin. This manuscript demonstrates feasibility in designing tunable thermosensitive hydrogels for loading multimodality therapeutic agents to enhance the bioactivity of leptin for obesity therapy.

SUBMITTER: Liao ZX

PROVIDER: S-EPMC5655123 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Light-triggered methylcellulose gold nanoparticle hydrogels for leptin release to inhibit fat stores in adipocytes.

Liao Zi-Xian ZX Liu Meng-Chia MC Kempson Ivan M IM Fa Yu-Chen YC Huang Kuo-Yen KY

International journal of nanomedicine 20171017

Leptin is released in response to increased triglyceride storage in adipocytes and impacts body weight, but has drawbacks such as poor therapeutic effect and side effects when delivered systemically. Leptin also modifies adipocyte sensitivity to insulin to inhibit lipid accumulation. Here, light-triggered degradation of hydrogels was used to improve accuracy and effectiveness for sustained and controllable release. In our approach, leptin was entrapped within methylcellulose (MC)-based hydrogels ...[more]

PMID: 29089758

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Project description:White adipose tissue (WAT) is essential for energy storage as well as being an active endocrine organ. The secretion of adipokines by adipocytes can affect whole body metabolism, appetite, and contribute to overall health. WAT is comprised of lipid-laden mature adipocytes, as well as immune cells, endothelial cells, pre-adipocytes, and adipose-derived stem cells. In addition, the presence of extracellular matrix (ECM) proteins in WAT can actively influence adipocyte differentiation, growth, and function. Type I collagen is an abundant fibrous ECM protein in WAT that is secreted by developing adipocytes. However, the extent and overall effect of Type I collagen on adipokine secretion in mature adipocytes when added exogenously has not been established.We characterized the effects of Type I collagen overlays prepared using two different buffers on adipocyte physiology and function when added at different times during differentiation. In addition, we compared the effect of collagen overlays when adipocytes were cultured on two different tissue culture plastics that have different adherent capabilities. Triglyceride accumulation was analyzed to measure adipocyte physiology, and leptin and adiponectin secretion was determined to analyze effects on adipokine secretion.We found that collagen overlays, particularly when added during the early differentiation stage, impaired adipokine secretion from mature adipocytes. Collagen prepared using PBS had a greater suppression of leptin than adiponectin while collagen prepared using HANKS buffer suppressed the secretion of both adipokines. The use of CellBind plates further suppressed leptin secretion. Triglyceride accumulation was not substantially impacted with any of the collagen overlays.Adipokine secretion can be selectively altered by collagen overlays. Thus, it is feasible to selectively manipulate the secretion of adipokines by adipocytes in vitro by altering the composition or timing of collagen overlays. The use of this technique could be applied to studies of adipokine function and secretion in vitro as well as having potential therapeutic implications to specifically alter adipocyte functionality in vivo.

Project description:Background: Leptin is an adipokine with well-known effects on the central nervous system including the induction of energy expenditure and satiety. Leptin also has major relevance when activating immune cells and modulating inflammatory response. In obesity, increases in white adipose tissue accumulation and leptin levels are accompanied by hypothalamic resistance to leptin. Even though the adipose tissue is a leptin-rich environment, the local actions of leptin regarding adipogenesis were not thoroughly investigated until now. Here we evaluate the contributions of leptins direct signaling in preadipocytes and adipose tissue-derived stromal cells (ASCs) for adipogenesis. Methods: Adipocytes were differentiated from the murine lineage of preadipocytes 3T3-L1 or ASCs from subcutaneous and visceral (retroperitoneal) fat depots from C57Bl/6J mice. Differentiating cells were treated with leptin in addition to or in replacement of insulin. The advance of adipogenesis was assessed by the expression and secretion of adipogenesis- and lipogenesis-related proteins by Western blot and immunoenzimatic assays, and the accumulation of lipid droplets by fluorescence microscopy. Results: Leptin treatment in 3T3-L1 preadipocytes or ASCs increased the production of the adipogenesis- and lipogenesis-related proteins PLIN1, CAV-1, PPARγ, SREBP1C, and/or adiponectin at earlier stages of differentiation. In 3T3-L1 preadipocytes, we found that leptin induced lipid droplets' formation in an mTOR-dependent manner. Also, leptin induced a proinflammatory cytokine profile in 3T3-L1 and ASCs, modulating the production of TNF-α, IL-10, and IL-6. Since insulin is considered an essential factor for preadipocyte differentiation, we asked whether leptin would support adipogenesis in the absence of insulin. Importantly, leptin induced the formation of lipid droplets and the expression of adipogenesis-related proteins independently of insulin during the differentiation of 3T3-L1 cells and ASCs. Conclusions: Our results demonstrate that leptin induces intracellular signaling in preadipocytes and adipocytes promoting adipogenesis and modulating the secretion of inflammatory mediators. Also, leptin restores adipogenesis in the absence of insulin. These findings contribute to the understanding of the local signaling of leptin in precursor and mature adipose cells. The proadipogenic role of leptin unraveled here may be of especial relevance during obesity, when its central signaling is defective.

Dataset Information

Light-triggered methylcellulose gold nanoparticle hydrogels for leptin release to inhibit fat stores in adipocytes.

Publications

Light-triggered methylcellulose gold nanoparticle hydrogels for leptin release to inhibit fat stores in adipocytes.

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