An obesogenic diet started before puberty leads to abnormal mammary gland development during pregnancy in the rabbit

Hue-Beauvais, Catherine; Chavatte‐Palmer, Pascale; Aujean, Etienne; Dahirel, Michèle; Laigre, P.; Péchoux, Christine; Bouet, Stéphan; Devinoy, Ève; Charlier, Madia

doi:10.1002/dvdy.22536

Cited by 24 publications

(29 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition, at 14 weeks of age, isolate-housed female FVB/N mice just after weaning, showed strikingly reduced mammary gland development compared to animals housed in standard conditions, as observed in our SE mice housed in standard laboratory cages [28]. These different models, including EE housing, demonstrate that mammary gland development is strongly influenced either by diet [29], [30] or by exposure to stress in early life and during adolescence [28]. Since both the hypothalamic-pituitary-adrenal (HPA) and -gonadal (HPG) axes appear to be modulated by environmentally challenging situations, including neonatal maternal separation or pubertal isolation, it is not surprising that EE can elicit long-lasting changes in mammary ductal development (Figure 8) [10], [27], [28].…”

Section: Discussionsupporting

confidence: 69%

Effects of Enriched Environment on COX-2, Leptin and Eicosanoids in a Mouse Model of Breast Cancer

et al. 2012

View full text Add to dashboard Cite

Cyclooxygenase-2 (COX-2) and adipokines have been implicated in breast cancer. This study investigated a possible link between COX-2 and adipokines in the development of mammary tumors. A model of environmental enrichment (EE), known to reduce tumor growth was used for a syngeneic murine model of mammary carcinoma. 3-week-old, female C57BL/6 mice were housed in standard environment (SE) or EE cages for 9 weeks and transplanted orthotopically with syngeneic EO771 adenocarcinoma cells into the right inguinal mammary fat pad. EE housing influenced mammary gland development with a decrease in COX-2 expressing cells and enhanced side-branching and advanced development of alveolar structures of the mammary gland. Tumor volume and weight were decreased in EE housed mice and were associated with a reduction in COX-2 and Ki67 levels, and an increase in caspase-3 levels. In tumors of SE mice, high COX-2 expression correlated with enhanced leptin detection. Non-tumor-bearing EE mice showed a significant increase in adiponectin levels but no change in those of leptin, F2-isoprostanes, PGF2α, IL-6, TNF-α, PAI-1, and MCP-1 levels. Both tumor-bearing groups (SE and EE housing) had increased resistin, IL-6, TNF-α, PAI-1 and MCP-1 levels irrespective of the different housing environment demonstrating higher inflammatory response due to the presence of the tumor. This study demonstrates that EE housing influenced normal mammary gland development and inhibited mammary tumor growth resulting in a marked decrease in intratumoral COX-2 activity and an increase in the plasma ratio of adiponectin/leptin levels.

show abstract

Section: Discussionsupporting

confidence: 69%

Effects of Enriched Environment on COX-2, Leptin and Eicosanoids in a Mouse Model of Breast Cancer

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Animal studies have shown that high-fat diet or obesity alters puberty onset (47, 48), mammary gland development and morphology (49–51), and tumor latency (9). Pubertal alterations including inflammatory cell composition, increased local production of growth factors, and angiogenesis may also contribute to the promotion of mammary carcinoma (52).…”

Section: Discussionmentioning

confidence: 99%

Weight Loss Reversed Obesity-Induced HGF/c-Met Pathway and Basal-Like Breast Cancer Progression

Sundaram

Essaid

et al. 2014

Front. Oncol.

View full text Add to dashboard Cite

Epidemiologic studies demonstrate that obesity is associated with an aggressive subtype of breast cancer called basal-like breast cancer (BBC). Using the C3(1)-TAg murine model of BBC, we previously demonstrated that mice displayed an early onset of tumors when fed obesogenic diets in the adult window of susceptibility. Obesity was also shown to elevate mammary gland expression and activation of hepatocyte growth factor (HGF)/c-Met compared to lean controls, a pro-tumorigenic pathway associated with BBC in patients. Epidemiologic studies estimate that weight loss could prevent a large proportion of BBC. We sought to investigate whether weight loss in adulthood prior to tumor onset would protect mice from accelerated tumorigenesis observed in obese mice. Using a life-long model of obesity, C3(1)-TAg mice were weaned onto and maintained on an obesogenic high-fat diet. Obese mice displayed significant elevations in tumor progression, but not latency or burden. Tumor progression was significantly reversed when obese mice were induced to lose weight by switching to a control low-fat diet prior to tumor onset compared to mice maintained on obesogenic diet. We investigated the HGF/c-Met pathway known to regulate tumorigenesis. Importantly, HGF/c-Met expression in normal mammary glands and c-Met in tumors was elevated with obesity and was significantly reversed with weight loss. Changes in tumor growth could not be explained by measures of HGF action including phospho-AKT or phospho-S6. Other mediators associated with oncogenesis such as hyperinsulinemia and a high leptin:adiponectin ratio were elevated by obesity and reduced with weight loss. In sum, weight loss significantly blunted the obesity-responsive pro-tumorigenic HGF/c-Met pathway and improved several metabolic risk factors associated with BBC, which together may have contributed to the dramatic reversal of obesity-driven tumor progression. Future research aims to evaluate the role of obesity and the HGF/c-Met pathway in basal-like breast cancer progression.

show abstract

“…Little is known about the impact that HFD consumption has on the mammary gland during lactation. Glucose transport into the mammary gland occurs through the GLUT1 transporter [40]. This is a critical step in the synthesis of lactose, the primary carbohydrate and osmotic constituent of milk.…”

Section: Discussionmentioning

confidence: 99%

“…This is a critical step in the synthesis of lactose, the primary carbohydrate and osmotic constituent of milk. GLUT1 is responsible for the delivery of glucose to the site of lactose synthesis [40]–[41]. Lactose is critical to human infants in particular in order to aid in temperature regulation by providing a large amount of free water to the neonate [42].…”

Section: Discussionmentioning

confidence: 99%

High Fat Diet Alters Lactation Outcomes: Possible Involvement of Inflammatory and Serotonergic Pathways

et al. 2012

View full text Add to dashboard Cite

Delay in the onset of lactogenesis has been shown to occur in women who are obese, however the mechanism altered within the mammary gland causing the delay remains unknown. Consumption of high fat diets (HFD) has been previously determined to result decreased litters and litter numbers in rodent models due to a decrease in fertility. We examined the effects of feeding a HFD (60% kcal from fat) diet versus a low-fat diet (LFD; 10% kcal from fat) to female Wistar rats on lactation outcomes. Feeding of HFD diet resulted in increased pup weights compared to pups from LFD fed animals for 4 d post-partum. Lactation was delayed in mothers on HFD but they began to produce copious milk volumes beginning 2 d post-partum, and milk yield was similar to LFD by day 3. Mammary glands collected from lactating animals on HFD diet, displayed a disrupted morphologies, with very few and small alveoli. Consistently, there was a significant decrease in the mRNA expression of milk protein genes, glucose transporter 1 (GLUT1) and keratin 5 (K5), a luminobasal cell marker in the mammary glands of HFD lactating animals. Expression of tryptophan hydroxylase 1 (TPH1), the rate-limiting enzyme in serotonin (5-HT) biosynthesis, and the 5-HT7 receptor (HTR7), which regulates mammary gland involution, were significantly increased in mammary glands of HFD animals. Additionally, we saw elevation of the inflammatory markers interleukin-6 (IL-6) and tumor necrosis factor-α (TNF- α). These results indicate that consumption of HFD impairs mammary parenchymal tissue and impedes its ability to synthesize and secrete milk, possibly through an increase in 5-HT production within the mammary gland leading to an inflammatory process.

show abstract

An obesogenic diet started before puberty leads to abnormal mammary gland development during pregnancy in the rabbit

Cited by 24 publications

References 43 publications

Effects of Enriched Environment on COX-2, Leptin and Eicosanoids in a Mouse Model of Breast Cancer

Effects of Enriched Environment on COX-2, Leptin and Eicosanoids in a Mouse Model of Breast Cancer

Weight Loss Reversed Obesity-Induced HGF/c-Met Pathway and Basal-Like Breast Cancer Progression

High Fat Diet Alters Lactation Outcomes: Possible Involvement of Inflammatory and Serotonergic Pathways

Contact Info

Product

Resources

About