Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
EMBO Rep ; 24(10): e55981, 2023 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-37560809

RESUMO

Accumulation of excess nutrients hampers proper liver function and is linked to nonalcoholic fatty liver disease (NAFLD) in obesity. However, the signals responsible for an impaired adaptation of hepatocytes to obesogenic dietary cues remain still largely unknown. Post-translational modification by the small ubiquitin-like modifier (SUMO) allows for a dynamic regulation of numerous processes including transcriptional reprogramming. We demonstrate that specific SUMOylation of transcription factor Prox1 represents a nutrient-sensitive determinant of hepatic fasting metabolism. Prox1 is highly SUMOylated on lysine 556 in the liver of ad libitum and refed mice, while this modification is abolished upon fasting. In the context of diet-induced obesity, Prox1 SUMOylation becomes less sensitive to fasting cues. The hepatocyte-selective knock-in of a SUMOylation-deficient Prox1 mutant into mice fed a high-fat/high-fructose diet leads to a reduction of systemic cholesterol levels, associated with the induction of liver bile acid detoxifying pathways during fasting. The generation of tools to maintain the nutrient-sensitive SUMO-switch on Prox1 may thus contribute to the development of "fasting-based" approaches for the preservation of metabolic health.

2.
Curr Opin Pharmacol ; 53: 101-116, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32871469

RESUMO

Obesity and cancer cachexia are diseases at opposite ends of the BMI. However, despite the apparent dichotomy, these pathologies share some common underlying mechanisms that lead to profound metabolic perturbations. Insulin resistance, adipose tissue lipolysis, skeletal muscle atrophy and systemic inflammation are key players in both diseases. Several strategies for pharmacological treatments have been employed in obesity and cancer cachexia but demonstrated only limited effects. Therefore, there is still a need to develop novel, more effective strategies. In this review we summarize existing therapies and discuss potential novel strategies that could arise by bridging common aspects between obesity and cachexia. We discuss the potential role of macrophage manipulation and the modulation of inflammation by targeting Nuclear Receptors (NRs) as potential novel therapeutic strategies.


Assuntos
Caquexia , Neoplasias , Obesidade , Animais , Regulação do Apetite , Caquexia/etiologia , Caquexia/imunologia , Caquexia/metabolismo , Caquexia/terapia , Humanos , Mediadores da Inflamação/imunologia , Macrófagos/imunologia , Neoplasias/complicações , Neoplasias/imunologia , Neoplasias/metabolismo , Neoplasias/terapia , Obesidade/imunologia , Obesidade/metabolismo , Obesidade/terapia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...