Lack of Peripheral Serotonin Protects Against Delayed Stage II Lactogenesis during High-Fat Diet Feeding

Program: Abstracts - Orals, Poster Previews, and Posters
Session: SUN 600-644-Energy Balance and Body Weight (posters)
Bench to Bedside
Sunday, April 3, 2016: 1:15 PM-3:15 PM
Exhibit/Poster Hall (BCEC)

Poster Board SUN 612
Justin Bohrer1, Samantha Weaver2, Allan Prichard1, Jake Olson1, Mark E Cook1 and Laura L Hernandez*2
1University of Wisconsin-Madison, 2University of Wisconsin-Madison, Madison, WI
Obesity is an established risk factor for the delayed onset of stage II lactogenesis.  Women who exhibit delayed lactogenesis II are less likely to successfully breast feed their children. Systemic inflammation is an important underlying component of obesity and is also stimulated under conditions of mammary gland involution. Serotonin has been shown to accelerate mammary gland involution.  Therefore, we hypothesized that obesity during lactation results in increased production of serotonin by the mammary gland, resulting in premature mammary gland involution.  To this end, we performed an experiment in which we fed female wild type (WT) mice and female mice deficient in the rate-limiting enzyme for serotonin synthesis (Tph1) one of two diets: low-fat diet (LFD; 10% Kcal fat) or a high-fat diet (HFD; 60% Kcal fat), beginning at 5 weeks of age through day 10 lactation.  Mice were mated after three weeks on their respective diets.  Maternal body weights and food intake were recorded weekly. Milk yield was recorded daily during lactation using the weigh-suckle-weigh method.  Milk was collected from mice daily to analyze fatty acid composition.  Mice were euthanized on d 10 of lactation and mammary glands were harvested for histology and gene expression analysis. WT mice on HFD produced significantly less milk than any other treatment group (P < 0.001). On d1 of lactation, WT HFD dams were unable to produce any milk (P < 0.0001) compared to all groups, while KO dams on both HFD and LFD were able to produce milk on d1 similar to that of WT LFD dams. Milk fatty acid composition was different between treatment groups (P<0.05) with HFD groups having more long-chain fatty acids and decreased de novo lipogenesis.  However, the WT HFD group had the highest content of 14:0 fatty acids compared to all treatment groups.   Immune markers have been demonstrated to be increased during mammary gland involution.  Therefore, we evaluated mRNA expression of several immune markers in the mammary gland.  mRNA expression of immune components Cxcl5 and Ccl22 were increased in the WT HFD group compared to WT LFD (P<0.05).  Ccl22 was also elevated in the KO LFD compared to the KO HFD (P<0.05), and the KO HFD was not different compared to the WT LFD (P>0.05) mRNA IFNg was increased in the WT HFD group compared to all other treatment groups (P<0.05).  Additionally, NOS2 expression was elevated in the KO LFD and WT HFD groups compared to the KO HFD and WT LFD groups (P<0.05). In conclusion, HFD feeding to WT mice delayed lactogenesis II, as seen by the inability to produce milk on d1 of lactation.  Furthermore, WT HFD mammary glands had more immune markers stimulated related to mammary gland involution compared to the other treatment groups. These effects appear to rescued by a deficiency in Tph1, preventing serotonergic activity. Serotonin may be an important component of the pathway that causes a deficiency in milk production at the onset of lactogenesis II in obese women.

Nothing to Disclose: JB, SW, AP, JO, MEC, LLH

*Please take note of The Endocrine Society's News Embargo Policy at