Involvement of the CXCL12 System in the Stimulatory Effects of Prenatal Exposure to High-Fat Diet on Hypothalamic
Kinning Poon1, Jessica R Barson1,2, Huanzhi Shi1
1Laboratory of Behavioral Neurobiology, Rockefeller UniversityNew York, NY, USA.
Insights
Prenatal high-fat diet (HFD) exposure increases the chemokine CXCL12 in dams and offspring, impacting brain development and anxiety. This suggests CXCL12 in the paraventricular nucleus may mediate HFD effects on behavior.
Area of Science:
- Neuroscience
- Developmental Biology
- Immunology
Background:
- Maternal high-fat diet (HFD) exposure during gestation impacts offspring neurodevelopment and behavior.
- Recent studies link HFD to increased inflammation, prompting investigation into neuroinflammatory mediators.
- The chemokine CXCL12 and its receptors (CXCR4, CXCR7) are implicated in neurodevelopment and inflammation.
Purpose of the Study:
- To investigate the role of the chemokine CXCL12 in mediating the effects of prenatal HFD exposure.
- To compare the effects of prenatal HFD exposure with direct prenatal CXCL12 administration on offspring neurobiology and behavior.
- To determine if HFD affects circulating CXCL12 in the dam and the CXCL12 system in the offspring brain.
Main Methods:
- Assessed circulating CXCL12 levels in dams exposed to HFD.
- Administered daily CXCL12 injections to pregnant dams.
- Measured CXCL12, CXCR4, and CXCR7 expression in the offspring hypothalamus (specifically the paraventricular nucleus - PVN).
- Evaluated neurogenesis and enkephalin (ENK) expression in the offspring PVN.
- Assessed anxiety-like behaviors in offspring using behavioral tests.
Main Results:
- Prenatal HFD exposure significantly increased circulating CXCL12 levels in dams.
- Prenatal HFD exposure increased CXCL12 and its receptors (CXCR4, CXCR7) expression in the offspring PVN.
- Both prenatal HFD and CXCL12 administration stimulated neurogenesis and ENK expression in the PVN.
- Both interventions increased anxiety-like behaviors in offspring, with effects being region-specific within the hypothalamus.
Conclusions:
- The CXCL12 chemokine system in the offspring PVN is potentially involved in mediating the effects of prenatal HFD exposure.
- Prenatal HFD and direct CXCL12 administration share similar neurobiological and behavioral outcomes, highlighting CXCL12's role.
- These findings suggest that targeting the CXCL12 system could be a strategy to mitigate adverse effects of maternal HFD on offspring neurodevelopment and emotional behavior.
Abstract:
Exposure to a high fat diet (HFD) during gestation stimulates neurogenesis and expression of hypothalamic orexigenic neuropeptides that affect consummatory and emotional behaviors. With recent studies showing a HFD to increase inflammation, this report investigated the neuroinflammatory chemokine, CXCL12, and compared the effects of prenatal CXCL12 injection to those of prenatal HFD exposure, first, by testing whether the HFD affects circulating CXCL12 in the dam and the CXCL12 system in the offspring brain, and then by examining whether prenatal exposure to CXCL12 itself mimics the effects of a HFD on hypothalamic neuropeptides and emotional behaviors. Our results showed that prenatal exposure to a HFD significantly increased circulating levels of CXCL12 in the dam, and that daily injections of CXCL12 induced a similar increase in CXCL12 levels as the HFD. In addition, prenatal HFD exposure significantly increased the expression of CXCL12 and its receptors, CXCR4 and CXCR7, in the hypothalamic paraventricular nucleus (PVN) of the offspring. Finally, the results revealed strong similarities in the effects of prenatal HFD and CXCL12 administration, which both stimulated neurogenesis and enkephalin (ENK) expression in the PVN, while having inconsistent or no effect in other regions of the hypothalamus, and also increased anxiety as measured by several behavioral tests. These results focus attention specifically on the CXCL12 chemokine system in the PVN of the offspring as being possibly involved in the stimulatory effects of prenatal HFD exposure on ENK-expressing neurons in the PVN and their associated changes in emotional behavior.
