Tart Cherry Juice and Seeds Affect Pro-Inflammatory Markers in Visceral Adipose Tissue of High-Fat Diet Obese Rats.

BACKGROUND: Tart cherries (Prunus cerasus L.) are a rich source of anthocyanins. They are phytochemical flavonoids found in red and blue fruits, and vegetables that can reduce hyperlipidemia. Visceral Adipose Tissue (VAT) has emerged as a major player in driving obesity-related inflammatory response. METHODS: This study has investigated the potential positive effects of tart cherries on rats with Diet-Induced Obesity (DIO). In particular, the inflammatory status in retroperitoneal (RPW) and perigonadal (PGW) adipose tissue were studied. Rats were fed ad libitum for 17 weeks with a hypercaloric diet with the supplementation of tart cherries seeds powder (DS) and seeds powder plus tart cherries juice containing 1mg of anthocyanins (DJS). In RPW and PGW, expression of CRP, IL-1 ß, TNF-α, CCL2 and CD36, were measured by qRT-PCR, Western blot and immunohistochemistry techniques. RESULTS: No differences in the weight of RPW and PGW animals were found between DS and DJS groups compared to DIO rats. However, an increase of inflammatory markers was observed in DIO group in comparison with control lean rats. A modulation of these markers was evident upon tart cherry supplementation. CONCLUSION: Study results suggest that tart cherry enriched-diet did not modify the accumulation of visceral fat, but it decreased inflammatory markers in both tissues. Therefore, this supplementation could be useful, in combination with healthy lifestyles, to modify adipose tissue cell metabolism limiting-obesity related organ damage.

Tart cherry (Prunus cerasus L.) dietary supplement modulates visceral adipose tissue CB1 mRNA levels along with other adipogenesis-related genes in rat models of diet-induced obesity.

PURPOSE: There is increasing evidence for the involvement of dietary bioactive compounds in the cross-talk modulation of endocannabinoid system and some of the key regulators of transcriptional control for adipogenesis. METHODS: We aimed to characterize the expression of cannabinoid CB1/CB2 receptors and fatty acid amide hydrolase (FAAH) along with selected adipogenesis-related genes (PPARγ, SREBP-1c and PREF-1), adipocyte-secreted factors (leptin and adiponectin), mitochondrial bioenergetic modulators (PGC-1A and UCP-2), and transient receptor potential vanilloid subtype 1 (TRPV1) and 2 (TRPV2) channels in visceral adipose tissue of rats fed with a high-fat diet (HFD) containing either tart cherry seeds alone or tart cherry seeds and juice for 17 weeks. The visceral adipose tissue was weighed and checked the expression of different markers by qRT-PCR, Western blot and immunohistochemistry. RESULTS: Tart cherry supplements were able to downregulate the HFD-induced mRNA expression of CB1 receptor, SREBP-1c, PPARγ, leptin, TRPV1 and TRPV2 resulting in potential anti-adipogenic effects. CONCLUSION: The present study points out that the intake of bioactive constituents of tart cherry may attenuate the effect of adipogenesis by acting directly on the adipose tissue and modulating the interplay between CB1, PPARγ and TRPV channel gene transcription.

The Melanocortin System behind the Dysfunctional Eating Behaviors.

The dysfunction of melanocortin signaling has been associated with obesity, given the important role in the regulation of energy homeostasis, food intake, satiety and body weight. In the hypothalamus, the melanocortin-3 receptor (MC3R) and melanocortin-4 receptor (MC4R) contribute to the stability of these processes, but MC3R and MC4R are also localized in the mesolimbic dopamine system, the region that responds to the reinforcing properties of highly palatable food (HPF) and where these two receptors seem to affect food reward and motivation. Loss of function of the MC4R, resulting from genetic mutations, leads to overeating in humans, but to date, a clear understanding of the underlying mechanisms and behaviors that promote overconsumption of caloric foods remains unknown. Moreover, the MC4R demonstrated to be a crucial modulator of the stress response, factor that is known to be strictly related to binge eating behavior. In this review, we will explore the preclinical and clinical studies, and the controversies regarding the involvement of melanocortin system in altered eating patterns, especially binge eating behavior, food reward and motivation.

Effects of Prunus cerasus L. Seeds and Juice on Liver Steatosis in an Animal Model of Diet-Induced Obesity.

The accumulation of adipose tissue increases the risk of several diseases. The fruits-intake, containing phytochemicals, is inversely correlated with their development. This study evaluated the effects of anthocyanin-rich tart cherries in diet-induced obese (DIO) rats. DIO rats were exposed to a high-fat diet with the supplementation of tart cherry seeds powder (DS) and seed powder plus juice (DJS). After 17 weeks, the DIO rats showed an increase of body weight, glycaemia, insulin, and systolic blood pressure. In the DS and DJS groups, there was a decrease of systolic blood pressure, glycaemia, triglycerides, and thiobarbituric reactive substances in the serum. In the DJS rats, computed tomography revealed a decrease in the spleen-to-liver attenuation ratio. Indeed, sections of the DIO rats presented hepatic injury characterized by steatosis, which was lower in the supplemented groups. In the liver of the DIO compared with rats fed with a standard diet (CHOW), a down-regulation of the GRP94 protein expression and a reduction of LC3- II/LC3-I ratio were found, indicating endoplasmic reticulum stress and impaired autophagy flux. Interestingly, tart cherry supplementation enhanced both unfolded protein response (UPR) and autophagy. This study suggests that tart cherry supplementation, although it did not reduce body weight in the DIO rats, prevented its related risk factors and liver steatosis.

Choline and Choline alphoscerate Do Not Modulate Inflammatory Processes in the Rat Brain.

Choline is involved in relevant neurochemical processes. In particular, it is the precursor and metabolite of acetylcholine (ACh). Choline is an essential component of different membrane phospholipids that are involved in intraneuronal signal transduction. On the other hand, cholinergic precursors are involved in ACh release and carry out a neuroprotective effect based on an anti-inflammatory action. Based on these findings, the present study was designed to evaluate the effects of choline and choline precursor (Choline alphoscerate, GPC) in the modulation of inflammatory processes in the rat brain. Male Wistar rats were intraperitoneally treated with 87 mg of choline chloride/kg/day (65 mg/kg/day of choline), and at choline-equivalent doses of GPC (150 mg/kg/day) and vehicle for two weeks. The brains were dissected and used for immunochemical and immunohistochemical analysis. Inflammatory cytokines (Interleukin-1ß, IL-1ß; Interleukin-6 , IL-6 and Tumor Necrosis Factor-α, TNF-α) and endothelial adhesion molecules (Intercellular Adhesion Molecule, ICAM-1 and Vascular cell Adhesion Molecule, VCAM-1) were studied in the frontal cortex, hippocampus, and cerebellum. The results clearly demonstrated that treatment with choline or GPC did not affect the expression of the inflammatory markers in the different cerebral areas evaluated. Therefore, choline and GPC did not stimulate the inflammatory processes that we assessed in this study.

Influence of dermal exposure to the pyrethroid insecticide deltamethrin on rat brain microanatomy and cholinergic/dopaminergic neurochemistry.

Deltamethrin is a pesticide largely used. Acute toxicity of this compound was extensively investigated, whereas less information is available on the effects of subchronic and/or chronic exposure to deltamethrin or on the effects of its dermal absorption. Sparse data are also available on deltamethrin neurotoxicity. This study has assessed in the rat the effects of dermal application of deltamethrin (30 mg/kg/day in cyclohexane for 4 weeks to the skin of the back of the neck) on microanatomy of cerebrocortical areas (frontal cortex and hippocampus) and on cholinergic and dopaminergic neurotransmission markers. Treatment with deltamethrin caused nerve cell loss and the appearance of signs of neuronal sufferance primarily in layer III of frontal cortex as well as in the dentate gyrus and to a lesser extent in the CA1 and CA3 subfields of hippocampus. Deltamethrin induced also astrogliosis. Cholinergic neurotransmission markers investigated in frontal cortex, hippocampus and striatum were acetylcholine (ACh), the synthesizing and catabolic enzymes choline acetyltransferase and acetylcholinesterase and the high affinity ACh uptake system labeled with [(3)H]hemicholinium-3. These markers were unaffected by deltamethrin administration. Dopamine and the dopamine plasma membrane transporter labeled with [(3)H]GBR 12935 were unaffected by treatment with deltamethrin in frontal cortex and decreased significantly in hippocampus and striatum. These findings indicate that dermal exposure to the pyrethroid insecticide deltamethrin using an administration module mimicking a possible long-lasting occupational skin contact is accompanied by cerebrocortical injury and loss of hippocampal and striatal dopamine and dopamine transporter. The sensitivity of dopaminergic system in our experimental model suggests that dermal exposure to deltamethrin could represent a risk factor for Parkinson's disease.

Neuroprotective effect of treatment with galantamine and choline alphoscerate on brain microanatomy in spontaneously hypertensive rats.

The present study was designed to assess if treatment with acetylcholinesterase inhibitor galantamine and the cholinergic precursor choline alphoscerate (alpha-glyceryl-phosphoryl-choline) alone or in association has any protective effect on brain microanatomy in spontaneously hypertensive rats (SHR) used as an animal model of vascular dementia (VaD). Thirty-two-week-old SHR and age-matched normotensive Wistar Kyoto (WKY) rats were left untreated or treated for 4 weeks with an oral dose of 3 mg/kg/day of galantamine, of 100 mg/kg/day of choline alphoscerate or their association. The number of neurons and of glial fibrillary acidic protein (GFAP) immunoreactive astrocytes, phosphorylated neurofilament, and microtubule associated protein-2 (MAP-2) and aquaporin-4 (AQP-4) was assessed by quantitative microanatomical and immunohistochemical techniques. In SHR, the number of neurons of frontal cortex, of the CA1 subfield of hippocampus and of dentate gyrus was decreased compared to WKY rats. Astrogliosis, breakdown of phosphorylated neurofilament, unchanged MAP-2 and altered AQP-4 expression were found as well. Both galantamine and choline alphoscerate countered nerve cell loss. Choline alphoscerate but not galantamine decreased astrogliosis and restored expression of AQ-4. Galantamine countered to a greater extent than choline alphoscerate phosphorylated neurofilament breakdown. The two drugs in association displayed a more remarkable effect. This study confirms a neuroprotective effect of galantamine in SHR and indicates a neuroprotective role of choline alphoscerate in the same model. A wider neuroprotective effect of the cholinergic inhibitor/precursor association was observed. These findings suggest to assess the activity of this cholinergic association in clinical trials.