Prolactin Promotes Adipose Tissue Fitness and Insulin Sensitivity in Obese Males

Ruíz-Herrera, Xarubet; Ríos, Ericka A. de los; Díaz, Juan Sánchez; Lerma-Alvarado, Ricardo M.; Escalera, Lucía Martínez de la; López-Barrera, Fernándo; Lemini, M. C. Cruz; Arnold, Edith; Escalera, Gonzálo Martínez de la; Clapp, Carmen; Macotela, Yazmín

doi:10.1210/en.2016-1444

Cited by 53 publications

(100 citation statements)

References 67 publications

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“…The effects of milk PRL in the offspring's adipose tissue are supported by our findings showing that oral PRL treatment to the neonatal offspring from HFD-fed mothers results in reduced VAT adiposity and increased subcutaneous adipocyte hyperplasia. In agreement, we have shown that in adult obese rats, PRL treatment promotes adipocyte hyperplasia while reducing visceral adipocyte hypertrophy (23).…”

Section: Discussionsupporting

confidence: 83%

Impaired prolactin actions mediate altered offspring metabolism induced by maternal high‐fat feeding during lactation

et al. 2018

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Maternal diet during lactation affects offspring metabolic health throughout life. Prolactin (PRL) is present in high quantities in maternal milk; however, the effects of milk PRL on the offspring remain poorly characterized. In this study, we evaluated whether feeding a high-fat diet (HFD) to rats during lactation alters PRL, both in the mother's serum and in milk, and whether this factor contributes to HFD-induced metabolic dysfunction in the offspring. Maternal HFD resulted in decreased PRL levels in milk (but not in serum), reduced mammary gland (MG) PRL receptor expression, and altered MG structure and function. Offspring from HFD-fed dams had increased body weight and adiposity, and developed fatty liver, hyperinsulinemia, and insulin resistance at weaning. Increasing PRL levels in the HFD-fed mothers by subcutaneous osmotic minipumps releasing PRL normalized MG function and PRL levels in milk. Moreover, PRL treatment in HFD-fed mothers, or directly in their pups via oral PRL administration, increased liver STAT5 phosphorylation, reduced visceral adiposity, ameliorated fatty liver, and improved insulin sensitivity in offspring. Our results show that HFD impairs PRL actions during lactation to negatively affect MG physiology and directly impair offspring metabolism.-De los Ríos, E. A., Ruiz-Herrera, X., Tinoco-Pantoja, V., López-Barrera, F., Martínez de la Escalera, G., Clapp, C., Macotela, Y. Impaired prolactin actions mediate altered offspring metabolism induced by maternal high-fat feeding during lactation.

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Section: Discussionsupporting

confidence: 83%

Impaired prolactin actions mediate altered offspring metabolism induced by maternal high‐fat feeding during lactation

et al. 2018

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“…In fact, several recent prospective studies suggested that the associations between prolactin and risk of type 2 diabetes and the metabolic syndrome were more likely to be beneficial in women but tended to be null or even detrimental in men [17–21]. The reason underlying this sex difference is unclear, as both beneficial and detrimental effects of prolactin on IR have been reported in men [12, 44]. Nevertheless, our data, coupled with prior evidence, suggest that prolactin may be related to pathogenic pathways leading to the development of type 2 diabetes in women.…”

Section: Discussionmentioning

confidence: 99%

“…Prolactin is a principal determinant of prenatal/postnatal development of pancreatic islet cells, as well as islet adaptation during pregnancy [5, 14, 20, 53]. It is also involved in the regulation of hepatic/adipocytic insulin sensitivity [12, 13], and can indirectly affect hypothalamic dopamine release and energy/glucose homeostasis [54]. In our study, prolactin was inversely correlated with C-peptide and adjusting for C-peptide attenuated the association between prolactin and type 2 diabetes (particularly for bioactive prolactin).…”

Section: Discussionmentioning

confidence: 99%

“…It also functions as an adipokine to regulate adipogenesis, lipid metabolism and inflammation [5, 6, 15]. Recent cross-sectional studies reported that higher circulating prolactin levels were associated with greater insulin sensitivity, lower glucose and lipid levels [12, 16, 17], and lower prevalence of diabetes and the metabolic syndrome [17, 18] (see electronic supplementary material [ESM] Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

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Circulating prolactin concentrations and risk of type 2 diabetes in US women

Rice

Huang

et al. 2018

Diabetologia

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Aims/hypothesis Prolactin, a multifunctional hormone, is involved in regulating insulin sensitivity and glucose homeostasis in experimental studies. However, whether circulating concentrations of prolactin are associated with risk of type 2 diabetes remains uncertain. Methods We analysed the prospective relationship between circulating prolactin concentrations and type 2 diabetes risk in the Nurses’ Health Study (NHS) and NHSII with up to 22 years of follow-up. Total plasma prolactin was measured using immunoassay in 8615 women free of type 2 diabetes and cardiovascular disease at baseline blood collection (NHS 1989–1990; NHSII 1996–1999) and a subset of 998 NHS women providing a second blood sample during 2000–2002. Baseline bioactive prolactin was measured in a subset of 2478 women using the Nb2 bioassay. HRs were estimated using Cox regression. Results A total of 699 incident type 2 diabetes cases were documented during 156,140 person- years of follow-up. Total plasma prolactin levels were inversely associated with type 2 diabetes risk; the multivariable HR comparing the highest with the lowest quartile was 0.73 (95% CI 0.55, 0.95; ptrend=0.02). The associations were similar by menopausal status and other risk factors (pinteraction>0.70). Additional adjustment for sex and growth hormones, adiponectin, and inflammatory and insulin markers did not significantly alter the results. The association of plasma bioactive prolactin with type 2 diabetes risk was non-significantly stronger than that of total prolactin (HR comparing extreme quartiles, 0.53 vs 0.81 among the subset of 2478 women, pdifference=0.11). The inverse association of total prolactin with type 2 diabetes was significant during the first 9 years after blood draw but waned linearly with time, whereas for bioactive prolactin, the inverse relationship persisted for a longer follow-up time after blood draw. Conclusions/interpretation A normally high circulating total prolactin concentration was associated with a lower type 2 diabetes risk within 9–10 years of follow-up since blood draw in US women. Our findings are consistent with experimental evidence, suggesting that among healthy women, prolactin within the biologically normal range may play a protective role in the pathogenesis of type 2 diabetes.

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“…Moreover, obese patients treated with bromocriptine or those with T2DM that did not show a substantial increase in prolactin levels, surprisingly still demonstrated an improvement in glucose control [49]. While remaining within the normal range, increased levels of prolactin have been suggested by several studies to reduce insulin resistance and the occurrence of T2DM [53][54][55]. In their study, Li et al attempted to evaluate whether healthy women with high prolactin levels were more protected from T2DM when compared to those with lower circulating prolactin.…”

Section: Managementmentioning

confidence: 99%

The Effect of Pituitary Gland Disorders on Glucose Metabolism: From Pathophysiology to Management

et al. 2020

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This review aims to explore, present, and discuss disorders of glucose metabolism implicated in pituitary gland diseases, the appropriate interventions, as well as the therapeutic challenges that may arise. Pituitary pathologies may dysregulate glucose homeostasis, as both the excess and deficiency of various pituitary hormones can affect glucose metabolism. Increased circulating levels of growth hormone, glucocorticoids or prolactin have been shown to mainly provoke hyperglycemic states, while hypopituitarism can be associated with both hyperglycemia and hypoglycemia. Addressing the primary cause of these disorders with the use of surgery, medical treatment or radiotherapy forms the cornerstone of current management strategies. Physicians should bear in mind that some such medications have an unfavorable effect on glucose metabolism too. When unsuccessful, or until the appropriate treatment of the underlying pituitary problem, the addition of established antidiabetic therapies might prove useful. Further studies aiming to discover more accurate and effective drug preparations in combination with optimal lifestyle management models will contribute to achieving a more successful glycemic control in these patients.

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Prolactin Promotes Adipose Tissue Fitness and Insulin Sensitivity in Obese Males

Cited by 53 publications

References 67 publications

Impaired prolactin actions mediate altered offspring metabolism induced by maternal high‐fat feeding during lactation

Impaired prolactin actions mediate altered offspring metabolism induced by maternal high‐fat feeding during lactation

Circulating prolactin concentrations and risk of type 2 diabetes in US women

The Effect of Pituitary Gland Disorders on Glucose Metabolism: From Pathophysiology to Management

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