Loss of myeloid lipoprotein lipase exacerbates adipose tissue fibrosis with collagen VI deposition and hyperlipidemia in leptin-deficient obese mice

Takahashi, Manabu; Yamamuro, Daisuke; Wakabayashi, T.; Takei, Akihito; Takei, Shoko; Nagashima, Shuichi; Okazaki, Hiroaki; Yagyu, Hiroaki; Takayanagi, Yuki; Onaka, Tatsushi; Goldberg, Ira J.; Ishibashi, Shun

doi:10.1016/j.jbc.2022.102322

Cited by 3 publications

(1 citation statement)

References 52 publications

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“…La leptina Tesis de Doctorado Lic. Ignacio Miguel 20 también ejerce un efecto en el metabolismo lipídico, si bien no resulta claro el mecanismo, se ha determinado que estimula la expresión de LPL 58,59 . En la Figura 5 se resume esquemáticamente la movilización lipídica en los adipocitos.…”

Section: Metabolismo Lipídico Del Tejido Adiposounclassified

Efecto de la ovariectomía prepuberal sobre la función del tejido adiposo blanco abdominal y subcutáneo

Miguel

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Nuestra hipótesis a ser puesta a prueba se basa en que “la castración prepuberal en la rata hembra provoca el desarrollo anormal del tejido adiposo blanco, lo cual genera un impacto en su funcionalidad, induciendo una respuesta disfuncional ante desafíos como ingestas ricas en fructosa o exposición al frío”. Objetivo general: Para responder nuestra hipótesis de trabajo, el objetivo general del presente proyecto será estudiar, en la rata hembra adulta sometida a castración prepuberal, las consecuencias de la castración a edad temprana, con principal foco en depósitos de tejido adiposo blanco: Tejido adiposo retroperitoneal (TARP) y Tejido adiposo inguinal (TAI), representantes de depósito abdominal y subcutáneo respectivamente. Adicionalmente, se estudiará la influencia de la castración a edad temprana en animales expuestos a una dieta obesogénica, como también la respuesta termogénica frente al estímulo de frío.

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Section: Metabolismo Lipídico Del Tejido Adiposounclassified

Efecto de la ovariectomía prepuberal sobre la función del tejido adiposo blanco abdominal y subcutáneo

Miguel

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Adipose tissue depot specific expression and regulation of fibrosis-related genes and proteins in experimental obesity

Eisinger,

Girke,

Buechler

et al. 2023

Mamm Genome

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Transforming growth factor beta (Tgfb) is a well-studied pro-fibrotic cytokine, which upregulates cellular communication network factor 2 (Ccn2), collagen, and actin alpha 2, smooth muscle (Acta2) expression. Obesity induces adipose tissue fibrosis, which contributes to metabolic diseases. This work aimed to analyze the expression of Tgfb, Ccn2, collagen1a1 (Col1a1), Acta2 and BMP and activin membrane-bound inhibitor (Bambi), which is a negative regulator of Tgfb signaling, in different adipose tissue depots of mice fed a standard chow, mice fed a high fat diet (HFD) and ob/ob mice. Principally, these genes were low expressed in brown adipose tissues and this difference was less evident for the ob/ob mice. Ccn2 and Bambi protein as well as mRNA expression, and collagen1a1 mRNA were not induced in the adipose tissues upon HFD feeding whereas Tgfb and Acta2 mRNA increased in the white fat depots. Immunoblot analysis showed that Acta2 protein was higher in subcutaneous and perirenal fat of these mice. In the ob/ob mice, Ccn2 mRNA and Ccn2 protein were upregulated in the fat depots. Here, Tgfb, Acta2 and Col1a1 mRNA levels and serum Tgfb protein were increased. Acta2 protein was, however, not higher in subcutaneous and perirenal fat of these mice. Col6a1 mRNA was shown before to be higher in obese fat tissues. Current analysis proved the Col6a1 protein was induced in subcutaneous fat of HFD fed mice. Notably, Col6a1 was reduced in perirenal fat of ob/ob mice in comparison to the respective controls. 3T3-L1 cells express Ccn2 and Bambi protein, whose levels were not changed by fatty acids, leptin, lipopolysaccharide, tumor necrosis factor and interleukin-6. All of these factors led to higher Tgfb in 3T3-L1 adipocyte media but did not increase its mRNA levels. Free fatty acids induced necrosis whereas apoptosis did not occur in any of the in vitro incubations excluding cell death as a main reason for higher Tgfb in cell media. In summary, Tgfb mRNA is consistently induced in white fat tissues in obesity but this is not paralleled by a clear increase of its target genes. Moreover, discrepancies between mRNA and protein expression of Acta2 were observed. Adipocytes seemingly do not contribute to higher Tgfb mRNA levels in obesity. These cells release more Tgfb protein when challenged with obesity-related metabolites connecting metabolic dysfunction and fibrosis.

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Interrelation of adipose tissue macrophages and fibrosis in obesity

Dahdah,

Tercero-Alcázar,

Malagón

et al. 2024

Biochemical Pharmacology

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Loss of myeloid lipoprotein lipase exacerbates adipose tissue fibrosis with collagen VI deposition and hyperlipidemia in leptin-deficient obese mice

Cited by 3 publications

References 52 publications

Efecto de la ovariectomía prepuberal sobre la función del tejido adiposo blanco abdominal y subcutáneo

Efecto de la ovariectomía prepuberal sobre la función del tejido adiposo blanco abdominal y subcutáneo

Adipose tissue depot specific expression and regulation of fibrosis-related genes and proteins in experimental obesity

Interrelation of adipose tissue macrophages and fibrosis in obesity

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