Effects of saturated versus unsaturated fatty acids on metabolism, gliosis, and hypothalamic leptin sensitivity in male mice

ABSTRACT

Background

Development of obesity and its comorbidities is not only the result of excess energy intake, but also of dietary composition. Understanding how hypothalamic metabolic circuits interpret nutritional signals is fundamental to advance towards effective dietary interventions.

Objective

We aimed to determine the metabolic response to diets enriched in specific fatty acids.

Methods

Male mice received a diet enriched in unsaturated fatty acids (UOLF) or saturated fatty acids (SOLF) for 8 weeks.

Results

UOLF and SOLF mice gained more weight and adiposity, but with no difference between these two groups. Circulating leptin levels increased on both fatty acid-enriched diet, but were higher in UOLF mice, as were leptin mRNA levels in visceral adipose tissue. In contrast, serum non-esterified fatty acid levels only rose in SOLF mice. Hypothalamic mRNA levels of NPY decreased and of POMC increased in both UOLF and SOLF mice, but only SOLF mice showed signs of hypothalamic astrogliosis and affectation of central fatty acid metabolism. Exogenous leptin activated STAT3 in the hypothalamus of all groups, but the activation of AKT and mTOR and the decrease in AMPK activation in observed in controls and UOLF mice was not found in SOLF mice.

Conclusions

Diets rich in fatty acids increase body weight and adiposity even if energy intake is not increased, while increased intake of saturated and unsaturated fatty acids differentially modify metabolic parameters that could underlie more long-term comorbidities. Thus, more understanding of how specific nutrients affect metabolism, weight gain, and obesity associated complications is necessary.

KEYWORDS:

• Saturated fatty acids
• monounsaturated fatty acids
• purified high-fat diets
• gliosis
• metabolism
• leptin resistance

Acknowledgements

We would like to thank Maria Jimenez and Sandra Canelles for their excellent technical support.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

All data are available upon request.

Additional information

Funding

This research was funded by grants from the Spanish Ministry of Science and Innovation (BFU2017-82565-C21-R2 to J.A.C. and L.M.F., BFU2016-78556-R and PID2020-117422RB-C21 to M.R-G, and BFU2017-82565-C2-2-R to B.S. and M.S.-F.A.), Centro de Investigación Biomédica en Red Fisiopatología de Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III Fondo de Investigación Sanitaria and Fondos FEDER (J.A.C.). Fundación Universitaria San Pablo-CEU, and FEDER. J.F-F. is supported by a grant from FUSP-CEU

Notes on contributors

Jesús Fernández-Felipe

Jesús Fernández-Felipe is a doctoral student in the Faculty of Pharmacy, Universidad San Pablo-CEU, Madrid.

Maria Valencia-Avezuela

Maria Valencia-Avezuela is now a doctoral student in the Instituto de Investigaciones Científicas Alberto Sols, CSIC, Madrid. This work was part of her Master’s Thesis at the Hospital Infantil Universitario Niño Jesús.

Beatriz Merino

Beatriz Merino is professor in the Faculty of Pharmacy, Universidad San Pablo-CEU, Madrid.

Beatriz Somoza

Beatriz Somoza is professor in the Faculty of Pharmacy, Universidad San Pablo-CEU, Madrid.

Victoria Cano

Victoria Cano is professor in the Faculty of Pharmacy, Universidad San Pablo-CEU, Madrid.

Ana B. Sanz-Martos

Ana B. Sanz-Martos is a doctoral student in the Faculty of Pharmacy, Universidad San Pablo-CEU, Madrid.

Laura M. Frago

Laura M. Frago is professor at the Faculty of Medicine, Universidad Autónoma de Madrid.

Maria S. Fernández-Alfonso

Maria S. Fernández-Alfonso is full professor in the Department of Pharmacy at the Universidad Complutense, Madrid.

Mariano Ruiz-Gayo

Mariano Ruiz-Gayo is full professor at the Faculty of Pharmacy, Universidad San Pablo-CEU, Madrid.

Julie A. Chowen

Julie A. Chowen is Senior Researcher at the Hospital Infantil Universitario Niño Jesús, Madrid.