Sex differences in response to a high fat, high sucrose diet in both the gut microbiome and hypothalamic astrocytes and microglia

ABSTRACT

Objectives: Obesity is a major epidemic in our population and has emerged as a primary health concern. Consumption of a high fat, high sugar (HFHS) diet can specifically lead to gut dysbiosis, increased inflammation, and neuroinflammation. Interestingly, sex differences in the response to a HFHS diet are emerging. In this study, we investigated the effects of a HFHS diet compared to a low fat, low sugar (LFLS) diet in 8 week old male and female C57Bl/6 mice.

Methods: The diet was administered for 14 weeks; body weights and food consumption were evaluated weekly.

Results: Male and female mice fed the HFHS diet gained significantly more weight than LFLS-fed mice. However, in agreement with previous studies, males gained significantly more weight on the HFHS diet compared to females fed the same diet. Importantly, we determined significant sex and diet-induced differences to gut microbiome composition using next generation Illumina sequencing. We also observed significantly less astrocyte densitometry and no significant change to microglial morphology in the hypothalamus of Female HFHS compared to Female LFLS. On the other hand, Male HFHS revealed no change to hypothalamic astrogliosis, but increased microgliosis compared to Male LFLS.

Discussion: In this study, we determined sex and diet-induced differences in both the gut and the brain, however, future studies will need to be performed in order to test the direct role of the gut microbiome to weight gain and neuroinflammation in male and female mice.

KEYWORDS:

• Diet-induced obesity
• inflammation
• gliosis
• gut microbiome
• sex differences

Acknowledgments

Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number P20GM103499 (LRF). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Disclosure statement

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

Additional information

Funding

Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under award number P20GM103499 (LRF).

Notes on contributors

Caroline M. Daly

Caroline M. Daly (Neuroscience) is an undergraduate student at Furman University and graduated in 2019. Caroline is currently attending medical school.

Juhi Saxena

Juhi Saxena (Neuroscience) is an undergraduate student at Furman University and graduated in 2019. Juhi is starting medical school this year.

Jagroop Singh

Jagroop Singh (Biology) is an undergraduate student at Furman University and graduated in 2019. Jagroop is starting medical school this year.

Meghan R. Bullard

Meghan R. Bullard is an undergraduate student studying Biology and German Studies; she will graduate in 2021.

Emma O. Bondy

Emma O. Bondy is an undergraduate student in the Neuroscience program at Furman University. Emma is graduating this year (2020).

Anju Saxena

Anju Saxena is an undergraduate student in the Neuroscience program at Furman University. Anju will graduate next year (2021).

Renata E. Buffalino

Renata E. Buffalino is an undergraduate student in the Neuroscience program at Furman University. Renata is graduating this year (2020).

Maria F. Melville

Maria F. Melville graduated from Benedict College in 2019 (Biology) and currently attends graduate school.

Linnea R. Freeman

Linnea R. Freeman is an Assistant Professor of Biology and Neuroscience at Furman University. She enjoys mentoring undergraduate students and is grateful for their hard work.