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Université de Fribourg

Obesity promotes the expansion of metastasis-initiating cells in breast cancer

Bousquenaud, Mélanie ; Fico, Flavia ; Solinas, Giovanni ; Rüegg, Curzio ; Santamaria-Martínez, Albert

In: Breast Cancer Research, 2018, vol. 20, no. 1, p. 104

Obesity is a strong predictor of poor prognosis in breast cancer, especially in postmenopausal women. In particular, tumors in obese patients tend to seed more distant metastases, although the biology behind this observation remains poorly understood.Methods: To elucidate the effects of the obese microenvironment on metastatic spread, we ovariectomized C57BL/6 J female mice and fed them...

Université de Fribourg

PI3Kγ activity in leukocytes promotes adipose tissue inflammation and early-onset insulin resistance during obesity

Breasson, Ludovic ; Becattini, Barbara ; Zani, Claudia Sardi†, Angela Molinaro†, Fabio ; Marone, Romina ; Botindari, Fabrizio ; Bousquenaud, Mélanie ; Ruegg, Curzio ; Wymann, Matthias P. ; Solinas, Giovanni

In: Science Signaling, 2017, vol. 10, no. 488, p. eaaf2969

The phosphoinositide 3-kinase γ (PI3Kγ) plays a major role in leukocyte recruitment during acute inflammation and has been proposed to inhibit classical macrophage activation by driving immunosuppressive gene expression. PI3Kγ plays an important role in diet-induced obesity and insulin resistance. In seeking to determine the underlying molecular mechanisms, we showed that PI3Kγ action in...

Université de Fribourg

JNK1 ablation in mice confers long-term metabolic protection from diet-induced obesity at the cost of moderate skin oxidative damage

Becattini, Barbara ; Zani, , Fabio ; Breasson, Ludovic ; Sardi, Claudia ; D'Agostino, Vito Giuseppe ; Choo, Min-Kyung ; Provenzani, Alessandro ; Park, Jin Mo ; Solinas, Giovanni

In: The FASEB Journal, 2016, vol. 30, no. 9, p. 3124–3132

Obesity and insulin resistance are associated with oxidative stress, which may be implicated in the progression of obesity-related diseases. The kinase JNK1 has emerged as a promising drug target for the treatment of obesity and type 2 diabetes. JNK1 is also a key mediator of the oxidative stress response, which can promote cell death or survival, depending on the magnitude and context of its...

Université de Fribourg

Inhibition of phosphoinositide 3-kinase γ attenuates inflammation, obesity, and cardiovascular risk factors

Wymann, Matthias P. ; Solinas, Giovanni

In: Annals of the New York Academy of Sciences, 2013, vol. 1280, p. 44-47

Phosphoinositide 3-kinase γ (PI3Kγ) plays a central role in inflammation, allergy, cardiovascular, and metabolic disease. Obesity is accompanied by chronic, low-grade inflammation. As PI3Kγ plays a major role in leukocyte recruitment, targeting of PI3Kγ has been considered to be a strategy for attenuating progression of obesity to insulin resistance and type 2 diabetes. Indeed, PI3Kγ null...

Université de Fribourg

A role for adipose tissue de novo lipogenesis in glucose homeostasis during catch-up growth : a randle cycle favoring fat storage

Marcelino, Helena ; Veyrat-Durebex, Christelle ; Summermatter, Serge ; Sarafian, Delphine ; Miles-Chan, Jennifer ; Arsenijevic, Denis ; Zani, Fabio ; Montani, Jean-Pierre ; Seydoux, Josiane ; Solinas, Giovanni ; Rohner-Jeanrenaud, Françoise ; Dulloo, Abdul G.

In: Diabetes, 2013, vol. 62, no. 2, p. 362-372

Catch-up growth, a risk factor for type 2 diabetes, is characterized by hyperinsulinemia and accelerated body fat recovery. Using a rat model of semistarvation-refeeding that exhibits catch-up fat, we previously reported that during refeeding on a low-fat diet, glucose tolerance is normal but insulin-dependent glucose utilization is decreased in skeletal muscle and increased in adipose tissue,...

Université de Fribourg

Molecular pathways linking metabolic inflammation and thermogenesis

Solinas, Giovanni

In: Obesity Review, 2012, vol. 13, no. S2, p. 69–82

Obesity is caused by chronic positive energy balance because of higher energy intake relative to energy expenditure. Thermogenesis, the capacity of an organism to produce heat, is an important component of energy expenditure. Thus targeting the molecular mechanisms controlling thermogenesis could be an effective strategy for the prevention or treatment of obesity. Thermogenesis is modulated by...

Université de Fribourg

High identification rates of endogenous neuropeptides from mouse brain

Zhang, Xiaozhe ; Petruzziello, Filomena ; Zani, Fabio ; Fouillen, Laetitia ; Andren, Per E. ; Solinas, Giovanni ; Rainer, Gregor

In: Journal of Proteome Research, 2012, vol. 11, no. 5, p. 2819–2827

Mass spectrometry-based neuropeptidomics is one of the most powerful approaches for identification of endogenous neuropeptides in the brain. Until now, however, the identification rate of neuropeptides in neuropeptidomics is relatively low and this severely restricts insights into their biological function. In the present study, we developed a high accuracy mass spectrometry-based approach to...

Université de Fribourg

Saturated fatty acids induce c-Src clustering within membrane subdomains, leading to JNK activation

Holzer, Ryan G. ; Park, Eek-Joong ; Li, Ning ; Tran, Helen ; Chen, Monica ; Choi, Crystal ; Solinas, Giovanni ; Karin, Michael

In: Cell, 2011, vol. 147, no. 1, p. 173–184

Saturated fatty acids (FA) exert adverse health effects and are more likely to cause insulin resistance and type 2 diabetes than unsaturated FA, some of which exert protective and beneficial effects. Saturated FA, but not unsaturated FA, activate Jun N-terminal kinase (JNK), which has been linked to obesity and insulin resistance in mice and humans. However, it is unknown how saturated and...

Université de Fribourg

PI3Kγ within a nonhematopoietic cell type negatively regulates diet-induced thermogenesis and promotes obesity and insulin resistance

Becattini, Barbara ; Marone, Romina ; Zani, Fabio ; Arsenijevic, Denis ; Seydoux, Josiane ; Montani, Jean-Pierre ; Dulloo, Abdul G. ; Thorens, Bernard ; Preitner, Frédéric ; Wymann, Matthias P. ; Solinas, Giovanni

In: Proceedings of the National Academy of Sciences of the United States of America, 2011, vol. 108, no. 42, p. E854-E863

Obesity is associated with a chronic low-grade inflammation, and specific antiinflammatory interventions may be beneficial for the treatment of type 2 diabetes and other obesity-related diseases. The lipid kinase PI3Kγ is a central proinflammatory signal transducer that plays a major role in leukocyte chemotaxis, mast cell degranulation, and endothelial cell activation. It was also reported that...

Université de Fribourg

Body composition phenotypes in pathways to obesity and the metabolic syndrome

Dulloo, Abdul G. ; Jacquet, Jean ; Solinas, Giovanni ; Montani, Jean-Pierre ; Schutz, Y.

In: International Journal of Obesity, 2010, vol. 34, p. S4–S17

Dynamic changes in body weight have long been recognized as important indicators of risk for debilitating diseases. While weight loss or impaired growth can lead to muscle wastage, as well as to susceptibility to infections and organ dysfunctions, the development of excess fat predisposes to type 2 diabetes and cardiovascular diseases, with insulin resistance as a central feature of the disease...