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Université de Fribourg

JNK1 and IKKβ: molecular links between obesity and metabolic dysfunction

Solinas, Giovanni ; Karin, Michael

In: The FASEB Journal, 2010, p. -

Inflammation is thought to underlie the pathogenesis of many chronic diseases. It is now established that obesity results in a state of chronic low-grade inflammation thought to contribute to several metabolic disorders, including insulin resistance and pancreatic islet dysfunction. The protein kinases JNK1 and IKKβ have been found to serve as critical molecular links between obesity, metabolic...

Université de Fribourg

Role of JNK activation in pancreatic β-cell death by streptozotocin

Cheon, Hwanju ; Cho, Jae Min ; Kim, Sunshin ; Baek, Seung-Hoon ; Lee, Moon-Kyu ; Kim, Kwang-Won ; Yu, Seong-Woon ; Solinas, Giovanni ; Kim, Soung Soo ; Lee, Myung-Shik

In: Molecular and Cellular Endocrinology, 2010, vol. 321, no. 2, p. 131-137

c-Jun N-terminal kinase (JNK) is activated by cellular stress and plays critical roles in diverse types of cell death. However, role of JNK in β-cell injury is obscure. We investigated the role for JNK in streptozotocin (STZ)-induced β-cell death. STZ induced JNK activation in insulinoma or islet cells. JNK inhibitors attenuated insulinoma or islet cell death by STZ. STZ-induced JNK activation...

Université de Fribourg

Adipose tissue plasticity during catch-up fat driven by thrifty metabolism: relevance for muscle-adipose glucose redistribution during catch-up growth

Summermatter, Serge ; Marcelino, Helena ; Arsenijevic, Denis ; Buchala, Antony J. ; Aprikian, Olivier ; Assimacopoulos-Jeannet, Françoise ; Seydoux, Josiane ; Montani, Jean-Pierre ; Solinas, Giovanni ; Dulloo, Abdul G.

In: Diabetes, 2009, vol. 58, no. 10, p. 2228-2237

OBJECTIVE: Catch-up growth, a risk factor for later type 2 diabetes, is characterized by hyperinsulinemia, accelerated body-fat recovery (catch-up fat), and enhanced glucose utilization in adipose tissue. Our objective was to characterize the determinants of enhanced glucose utilization in adipose tissue during catch-up fat. RESEARCH DESIGN AND METHODS: White adipose tissue morphometry, lipogenic...

Université de Fribourg

Thrifty metabolism that favors fat storage after caloric restriction: a role for skeletal muscle phosphatidylinositol-3-kinase activity and AMP-activated protein kinase

Summermatter, Serge ; Mainieri, Davide ; Russell, A. P. ; Seydoux, Josiane ; Montani, Jean-Pierre ; Buchala, Anthony J. ; Solinas, Giovanni ; Dulloo, Abdul G.

In: Faseb Journal, 2008, vol. 22, p. 774-785

Energy conservation directed at accelerating body fat recovery (or catch-up fat) contributes to obesity relapse after slimming and to excess fat gain during catch-up growth after malnutrition. To investigate the mechanisms underlying such thrifty metabolism for catch-up fat, we tested whether during refeeding after caloric restriction rats exhibiting catch-up fat driven by suppressed...

Université de Fribourg

Corticotropin-Releasing Hormone directly stimulates thermogenesis in skeletal muscle possibly through substrate cycling between de novo lipogenesis and lipid oxidation

Solinas, Giovanni ; Summermatter, Serge ; Mainieri, Davide ; Gubler, Marcel ; Montani, Jean-Pierre ; Seydoux, Josiane ; Smith, S. R. ; Dulloo, Abdul G.

In: Endocrinology, 2006, vol. 147(1), p. 31-38

The mechanisms by which CRH and related peptides (i.e. the CRH/urocortin system) exert their control over thermogenesis and weight regulation have until now focused only upon their effects on brain centers controlling sympathetic outflow. Using a method that involves repeated oxygen uptake determinations in intact mouse skeletal muscle, we report here that CRH can act directly on skeletal...

Université de Fribourg

The direct effect of leptin on skeletal muscle thermogenesis is mediated by substrate cycling between de novo lipogenesis and lipid oxidation

Solinas, Giovanni ; Summermatter, Serge ; Mainieri, Davide ; Gubler, Marcel ; Pirola, Luciano ; Wymann, Matthias P. ; Rusconi, Sandro ; Montani, Jean-Pierre ; Seydoux, Josiane

In: FEBS Letters, 2004, vol. 577, no. 3, p. 539-544

We report here studies that integrate data of respiration rate from mouse skeletal muscle in response to leptin and pharmacological interference with intermediary metabolism, together with assays for phosphatidylinositol 3-kinase (PI3K) and AMP- activated protein kinase (AMPK). Our results suggest that the direct effect of leptin in stimulating thermogenesis in skeletal muscle is mediated by...

Université de Fribourg

Substrate cycling between de novo lipogenesis and lipid oxidation: a thermogenic mechanism against skeletal muscle lipotoxicity and glucolipotoxicity

Dulloo, Abdul G. ; Gubler, Marcel ; Montani, Jean-Pierre ; Seydoux, Josiane ; Solinas, Giovanni

In: International Journal of Obesity, 2004, vol. 28 (Suppl. 4), p. S29-S37

Life is a combustion, but how the major fuel substrates that sustain human life compete and interact with each other for combustion has been at the epicenter of research into the pathogenesis of insulin resistance ever since Randle proposed a 'glucose-fatty acid cycle' in 1963. Since then, several features of a mutual interaction that is characterized by both reciprocality and dependency between...