Drugs Affecting Membrane Lipid Catabolism: The Brain Free Fatty Acid Effect

Author(s):  
Elena B. Rodriguez de Turco
1994 ◽  
Vol 47 (2) ◽  
pp. 415-417 ◽  
Author(s):  
Pascal Claudepierre ◽  
Saïk Urien ◽  
Olivier Chassany ◽  
Jean-Paul Tillement

2015 ◽  
Vol 35 (6) ◽  
pp. 2272-2284 ◽  
Author(s):  
Tina Sartorius ◽  
Andrea Drescher ◽  
Madhura Panse ◽  
Petr Lastovicka ◽  
Andreas Peter ◽  
...  

Background/Aims: Conjugated linoleic acids (CLAs) affect body fat distribution, induce insulin resistance and stimulate insulin secretion. The latter effect is mediated through the free fatty acid receptor-1 (GPR40/FFAR1). This study examines whether GPR40/FFAR1 interacts with tissue specific metabolic changes induced by CLAs. Methods and Results: After chronic application of CLAs C57BL/6J wild type (WT) and GPR40/FFAR1 (Ffar1-/-) knockout mice developed insulin resistance. Although CLAs accumulated in liver up to 46-fold genotype-independently, hepatic triglycerides augmented only in WT mice. This triglyceride deposition was not associated with increased inflammation. In contrast, in brain of CLA fed Ffar1-/- mice mRNA levels of TNF-α were 2-fold higher than in brain of WT mice although CLAs accumulated genotype-independently in brain up to 4-fold. Concomitantly, Ffar1-/- mice did not respond to intracerebroventricular (i.c.v.) insulin injection with an increase in cortical activity while WT mice reacted as assessed by radiotelemetric electrocorticography (ECoG) measurements. In vitro incubation of primary murine astrocytes confirmed that CLAs stimulate neuronal inflammation independent of GPR40/FFAR1. Conclusion: This study discloses that GPR40/FFAR1 indirectly modulates organ-specific effects of CLAs: the expression of functional GPR40/FFAR1 counteracts CLA-induced inflammation and insulin resistance in the brain, but favors the development of fatty liver.


2019 ◽  
Vol 160 (45) ◽  
pp. 1774-1783 ◽  
Author(s):  
Tamás Halmos ◽  
Ilona Suba

Abstract: The existence of insulin-like growth factors (IGFs) was recognized in connection with the stimulation of sulfate incorporation into cartilage. IGFs take part in the embryonal development and postnatal growth, in interaction with the growth hormone (GH). The physiological effects of IGF1 are promotion of tissue growth and development, stimulation of cell proliferation, effects on lipid and carbohydrate metabolism, anti-aging, anti-inflammatory, anabolic, anti-oxidant, neuro- and hepatoprotective properties. Our knowledge about the GH/IGF axis is diverse, partly contradictory, their research is continued intensively nowadays. We considered it worthwhile to review and interpret this information. Study on GH/IGF medical reports, with particular reference to the less known metabolic control. 75% of the growth factors are produced in the liver by GH and insulin stimulation; their effects are expressed on specific receptors, and modified by specific binding proteins. IGF1 directly increases the muscle mass, bone density, and the structure of the bones. Intestinal microbiota induces secretion of IGF1, which promotes the development and remodeling of the bones. Short-chain fatty acids, produced in microbial fermented fibers, induce secretion of IGF1, suggesting that microbial activity also affects bone health via IGF1. IGF1 also has a direct and indirect glucose-lowering effect, enhances free fatty acid oxidation in the muscle, reducing the flow of free fatty acid into the liver, improving insulin signaling, resulting in the reduction of hepatic glucose output, and improves insulin sensitivity. IGF1 directly influences the expression of circadian BMAL1 in hypothalamic cells: this refers to the newly recognized ’zeitgeber’ role of IGF1. The bioactivity of insulin-like peptides in the brain is characterized by neuronal survival, excitatory and inhibitory neurotransmission, maintenance of normal free fatty acid levels, improvement of cognitive function, protection against cell damage, neurogenesis and angiogenesis. The effects of IGF2 are less outlined, however, it has a relevant role in the development of the fetus, and acts protectively on the brain. Lack or over-expression of IGF1 can be detected or may causally associated in many pathological conditions. According to these collected data, insulin sensitivity may be improved by different pathways. The role of IGFs in these processes should be a task of future research. Orv Hetil. 2019; 160(45): 1774–1783.


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