Leptin signal transduction underlies the differential metabolic response of LEW and WKY rats to cafeteria diet

Martínez-Micaelo, Neus; González-Abuín, Noemi; Ardévol, Anna; Pinent, Montserrat; Petretto, Enrico; Behmoaras, Jacques; Blay, Mayte

doi:10.1530/jme-15-0089

Cited by 7 publications

(10 citation statements)

References 33 publications

(38 reference statements)

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“…1. Experimental design used to study the role of inbred rat models in nutritional genomics. The phenotypic response (described previously in Martínez-Micaelo et al, 2016) shows a differential susceptibility of LEW and WKY rats to the CAF diet. Here, we studied the differential modulation of the peripheral monocyte transcriptome of LEW and WKY rats by the CAF diet, as consequence of the prone and resistant responses of LEW and WKY rats, respectively, to the diet-induced obesity.…”

Section: Resultsmentioning

confidence: 64%

“…Based on our previous results (Martínez-Micaelo et al, 2016), although both strains showed increased weight gain and adiposity in response to the CAF diet, plasma metabolic profiling evidenced contrasting phenotypic responses. Indeed, CAF diet challenge induced hyperglycaemia, hypertriglyceridaemia and higher levels of NEFAs in LEW rats, which was not the case for WKY rats.…”

Section: Discussionmentioning

confidence: 71%

“…We have previously shown in detail strain-specific phenotypic differences in CAF-diet-induced obesity in LEW and WKY rats (Martínez-Micaelo et al, 2016). Strain-specific differences were also observed in the modulation of the circulating levels of inflammatory biomarkers.…”

Section: Resultsmentioning

confidence: 99%

“…See Fig. 1 and Martínez-Micaelo et al (2016) for more detailed experimental design. Heparinised plasma was obtained by centrifugation from blood samples and stored at −80°C until analysis.…”

Section: Methodsmentioning

confidence: 99%

“…Hence, by comparing the responses of Lewis (LEW) and Wistar Kyoto (WKY) rats to an obesogenic diet, we recently showed significant differences in metabolic and morphometric parameters (Martínez-Micaelo et al, 2016). Specifically, our results suggested the leptin signalling pathway as a divergent point between the strain-specific adaptations to CAF diet.…”

Section: Introductionmentioning

confidence: 99%

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Identification of a nutrient sensing transcriptional network in monocytes by using inbred rat models of cafeteria diet

Martínez-Micaelo

González-Abuín

Terra

et al. 2016

Disease Models &Amp; Mechanisms

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Obesity has reached pandemic levels worldwide. The current models of diet-induced obesity in rodents use predominantly high-fat based diets that do not take into account the consumption of variety of highly palatable, energy-dense foods that are prevalent in Western society. We and others have shown that the cafeteria (CAF) diet is a robust and reproducible model of human metabolic syndrome with tissue inflammation in the rat. We have previously shown that inbred rat strains such as Wistar Kyoto (WKY) and Lewis (LEW) show different susceptibilities to CAF diets with distinct metabolic and morphometric profiles. Here, we show a difference in plasma MCP-1 levels and investigate the effect of the CAF diet on peripheral blood monocyte transcriptome, as powerful stress-sensing immune cells, in WKY and LEW rats. We found that 75.5% of the differentially expressed transcripts under the CAF diet were upregulated in WKY rats and were functionally related to the activation of the immune response. Using a gene co-expression network constructed from the genes differentially expressed between CAF diet-fed LEW and WKY rats, we identified acyl-CoA synthetase short-chain family member 2 (Acss2) as a hub gene for a nutrient-sensing cluster of transcripts in monocytes. The Acss2 genomic region is significantly enriched for previously established metabolism quantitative trait loci in the rat. Notably, monocyte expression levels of Acss2 significantly correlated with plasma glucose, triglyceride, leptin and non-esterified fatty acid (NEFA) levels as well as morphometric measurements such as body weight and the total fat following feeding with the CAF diet in the rat. These results show the importance of the genetic background in nutritional genomics and identify inbred rat strains as potential models for CAF-diet-induced obesity.

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Section: Resultsmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 71%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Identification of a nutrient sensing transcriptional network in monocytes by using inbred rat models of cafeteria diet

Martínez-Micaelo

González-Abuín

Terra

et al. 2016

Disease Models &Amp; Mechanisms

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Epoxygenase inactivation exacerbates diet and aging-associated metabolic dysfunction resulting from impaired adipogenesis

Olona

Terra

et al. 2018

Molecular Metabolism

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ObjectiveWhen molecular drivers of healthy adipogenesis are perturbed, this can cause hepatic steatosis. The role of arachidonic acid (AA) and its downstream enzymatic cascades, such as cyclooxygenase, in adipogenesis is well established. The exact contribution of the P450 epoxygenase pathway, however, remains to be established. Enzymes belonging to this pathway are mainly encoded by the CYP2J locus which shows extensive allelic expansion in mice. Here we aimed to establish the role of endogenous epoxygenase during adipogenesis under homeostatic and metabolic stress conditions.MethodsWe took advantage of the simpler genetic architecture of the Cyp2j locus in the rat and used a Cyp2j4 (orthologue of human CYP2J2) knockout rat in two models of metabolic dysfunction: physiological aging and cafeteria diet (CAF). The phenotyping of Cyp2j4−/− rats under CAF was integrated with proteomics (LC-MS/MS) and lipidomics (LC-MS) analyses in the liver and the adipose tissue.ResultsWe report that Cyp2j4 deletion causes adipocyte dysfunction under metabolic challenges. This is characterized by (i) down-regulation of white adipose tissue (WAT) PPARγ and C/EBPα, (ii) adipocyte hypertrophy, (iii) extracellular matrix remodeling, and (iv) alternative usage of AA pathway. Specifically, in Cyp2j4−/− rats treated with a cafeteria diet, the dysfunctional adipogenesis is accompanied by exacerbated weight gain, hepatic lipid accumulation, and dysregulated gluconeogenesis.ConclusionThese results suggest that AA epoxygenases are essential regulators of healthy adipogenesis. Our results uncover their synergistic role in fine-tuning AA pathway in obesity-mediated hepatic steatosis.

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D-arabinose acts as antidepressant by activating the ACSS2-PPARγ/TFEB axis and CRTC1 transcription

Guo,

Chen,

Zhao

et al. 2024

Pharmacological Research

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Leptin signal transduction underlies the differential metabolic response of LEW and WKY rats to cafeteria diet

Cited by 7 publications

References 33 publications

Identification of a nutrient sensing transcriptional network in monocytes by using inbred rat models of cafeteria diet

Identification of a nutrient sensing transcriptional network in monocytes by using inbred rat models of cafeteria diet

Epoxygenase inactivation exacerbates diet and aging-associated metabolic dysfunction resulting from impaired adipogenesis

D-arabinose acts as antidepressant by activating the ACSS2-PPARγ/TFEB axis and CRTC1 transcription

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