Fatty acid metabolism as a target for obesity treatment

Ronnett, Gabriele V.; Kim, Eun Kyoung; Landree, Leslie E.; Tu, Yajun

doi:10.1016/j.physbeh.2005.04.014

Cited by 112 publications

(78 citation statements)

References 96 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Activation of AMPK enhances ATPgenerating, catabolic pathways and inhibits lipid, fatty acid, cholesterol, and protein synthesis through phosphorylation of key regulatory proteins leading to increased ATP availability (Li and McCullough 2010). Compound C reduces ATPgeneration by inhibiting AMPK in vitro (Ronnett et al 2005). This was confirmed in the present study as Compound C significantly decreased ATP pro-duction compared with vehicle-treated group (Fig.…”

Section: Discussionsupporting

confidence: 82%

Age-related changes in AMP-activated protein kinase after stroke

Liu

Benashski

Persky

et al. 2011

AGE

View full text Add to dashboard Cite

Adenosine monophosphate-activated protein kinase (AMPK) is an evolutionary conserved energy sensor sensitive to changes in cellular AMP/ ATP ratio which is activated by phosphorylation (pAMPK). pAMPK levels decrease in peripheral tissues with age, but whether this also occurs in the aged brain, and how this contributes to the ability of the aged brain to cope with ischemic stress is unknown. This study investigated the activation of AMPK and the response to AMPK inhibition after induced stroke in both young and aged male mice. Baseline levels of phosphorylated AMPK were higher in aged brains compared to young mice. Strokeinduced a robust activation of AMPK in young mice, yet this response was muted in the aged brain. Young mice had larger infarct volumes compared with aged animals; however, more severe behavioral deficits and higher mortality were seen in aged mice after stroke. Inhibition of AMPK with Compound C decreased infarct size in young animals, but had no effect in aged mice. Compound C administration led to a reduction in brain ATP levels and induced hypothermia, which led to enhanced neuroprotection in young but not aged mice. This work demonstrates that aging increases baseline brain pAMPK levels; aged mice have a muted stroke-induced pAMPK response; and that AMPK inhibition and hypothermia are less efficacious neuroprotective agents in the aged brain. This has important translational relevance for the development of neuroprotective agents in preclinical models and our understanding of the enhanced metabolic stress experienced by the aged brain.

show abstract

Section: Discussionsupporting

confidence: 82%

Age-related changes in AMP-activated protein kinase after stroke

Liu

Benashski

Persky

et al. 2011

AGE

View full text Add to dashboard Cite

show abstract

“…The two components integrate several circulating factors of hunger and satiety and communicate with one another to adapt both metabolic demands and the hedonic and motivational aspect of food intake. Although it is generally accepted that the brain does not uses lipids as a primary source of energy, it expresses several enzymes involved in the transport, hydrolysis and manipulation of TG-rich particle and LCFAs (Kim et al, 2002;Ronnett et al, 2005;Ronnett et al, 2006). Central LCFAs sensing in the hypothalamus was recently demonstrated to be a key mechanism for the homeostatic regulation of food intake Migrenne et al, 2011).…”

Section: Resultsmentioning

confidence: 99%

“…C75 also increases energy consumption, which contributes to weight loss. In vitro and in vivo studies demonstrate that at least part of C75's effects are mediated by the modulation of AMP kinase (AMPK), a known peripheral energy-sensing kinase (Ronnett et al, 2005). Indeed, ICV.…”

Section: Hypothalamic Sensing Of Lcfas and Metabolic Syndromementioning

confidence: 99%

“…Elevated circulating levels of long-chain fatty acids (LCFAs), which are often elevated in obese and diabetic individuals, have recently been demonstrated to be an important signaling molecule acting in the hypothalamus to control food intake and energy expenditure (Kim et al, 2002;Ronnett et al, 2005;Ronnett et al, 2006). In addition, component of the reward circuitry also expresses several enzymes involved in the processing of triglyceride and fatty acid including lipoprotein lipase (LPL) (Ben-Zeev et al, 1990;Paradis et al, 2004), an enzyme responsible for triglyceride hydrolysis.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Central lipid detection and the regulation of feeding behavior

Cansell¹,

Luquet²

2013

OCL

View full text Add to dashboard Cite

“…Both mesolimbic and hypothalamic regions express enzymes involved in the transport, manipulation and metabolism of TG (Eckel and Robbins, 1984;Kim et al, 2002;Paradis et al, 2004;Rapoport, 2001;Ronnett et al, 2005Ronnett et al, , 2006Eckel, 2009, 2012). In particular, the HP and the Nacc express LPL, a key enzyme involved in TG hydrolysis (Ben-Zeev et al, 1990).…”

Section: Mesolimbic Triglycerides Sensingmentioning

confidence: 99%

Mesolimbic lipid sensing and the regulation of feeding behaviour

Cansell

Luquet²

2015

OCL

View full text Add to dashboard Cite

-In both developed and emerging countries, sedentary life style and over exposition to high energy dense foods has led to a thermodynamic imbalance and consequently obesity. Despite genetic predisposition, obesity often involves a behavioral component in which, similar to drugs of abuse, compulsive consumption of palatable food rich in lipids and sugar drives energy intake far beyond metabolic demands. Food intake is modulated by sensory inputs, such as tastes and odours, as well as by affective or emotional states. The mesolimbic pathway is well established as a main actor of the rewarding aspect of feeding. Particularly, the hedonic and motivational aspects of food are closely tied to the release of the neurotransmitter dopamine (DA) in striatal structure such as the Nucleus Accumbens (Nacc). In both rodent and humans several studies shows an attenuated activity of dopaminergic signal associated with obesity and there is evidence that consumption of palatable food per se leads to DA signalling alterations. Furthermore impaired cognition in obese mice is improved by selectively lowering triglycerides (TG) and intracerebroventricular administration of TG induces by itself acquisition impairment in several cognitive paradigms in normal body weight mice. Together, these observations raise the possibility that nutritional lipids, particularly TG, directly affect cognitive and reward processes by modulating the mesolimbic pathway and might contribute to the downward spiral of compulsive consumption of palatable and obesity. This review is an attempt to capture recent evolution in the field that might point toward a direct action of nutritional lipid in the mesolimbic pathway.Keywords: Obesity / tryglicerides / feeding behavior / reward / lipoprotein lipase Résumé -La détection des lipides par le système mésolimbique et la régulation des comportements alimentaires. Dans les pays développés et en voie de développement la sédentarisation des populations et la surexposition aux nourritures riche en énergie conduisent à la mise en place d'un déséquilibre énergétique et à l'obésité. Bien qu'il existe des prédispositions génétiques, l'obésité implique souvent des comportements compulsifs face à la nourriture, similaires aux drogues d'abus, qui entraînent une consommation de nourriture supérieure aux besoins éner-gétiques de l'organisme. L'hypothalamus est le premier site d'intégration des facteurs circulants qui reflètent le statut énergétique de l'organisme, il est donc considéré comme un des acteurs principaux dans la régulation centrale de la balance énergétique. Cependant, la prise alimentaire est également régulée par des facteurs sensoriels ou affectifs et le système mesolimbique est reconnu pour être un des systèmes majeurs dans la régulation de récompense associée à la prise alimentaire. Plus spécifiquement, les aspects motivationnels et hédoniques de la prise alimentaire sont étroitement liés à la libération de dopamine (DA) notamment dans le noyau accumbens. Plusieurs études montrent qu'à la fois chez l'...

show abstract

Fatty acid metabolism as a target for obesity treatment

Cited by 112 publications

References 96 publications

Age-related changes in AMP-activated protein kinase after stroke

Age-related changes in AMP-activated protein kinase after stroke

Central lipid detection and the regulation of feeding behavior

Mesolimbic lipid sensing and the regulation of feeding behaviour

Contact Info

Product

Resources

About