Delta‐like protein 1 in the pituitary‐adipose axis in the adult male mouse

Abstract

With the aim of studying delta‐like protein 1 (DLK1) with respect to the relationship between adipocyte leptin and adenohypophyseal hormones, we carried out an immunohistochemical study analysing the presence of receptors for these hormones in the pituitary and adipose cells of male wild‐type (WT) mice (Dlk1 +/+) compared to knockout (KO) mice (Dlk1 −/−). The mRNA expression of these molecules was also determined using the reverse transcriptase‐polymerase chain reaction. The results obtained showed that, in WT adipose cells, all of the adenohypophyseal hormone receptors were present, with a higher mRNA expression for growth hormone (GH) receptor and thyroid‐stimulating hormone (TSH) receptor. Of the total cells in the anterior pituitary lobe, 17.09±0.9% were leptin receptor (LEPR) immunoreactive (‐IR), mainly in GH‐IR and prolactin (PRL)‐IR cells (41.5±3.8%; 13.5±1.7%, respectively). In Dlk1 −/− mice, adipocyte cells showed a significant increase in the TSH receptor mRNA expression level. Moreover, the percentage of LEPR‐IR GH cells showed a statistically significant increase compared to controls, from 41.5±3.8% to 53.1±4.0%. By contrast, only 3.0±0.6% of LEP‐IR anterior pituitary cells were detected in Dlk1 KO mice, as opposed to 6.8±1.1% observed in WT mice. The results suggest that relationships exist between adipocytes and pituitary GH, PRL and TSH cells, in addition to an influence with respect to the synthesis and release of pituitary leptin, particularly in PRL cells.

Clinical correlates and metabolic indicators of elevated fasting glucose in overweight/obese Chinese Han patients with first-episode and drug-naive major depressive disorder

“…The reasons and mechanisms for this phenomenon may be as follows: First, the concentration of 5-hydroxytryptamine in the brain is reduced in patients with major depression, leading to an increase in the concentration of thyrotropin-releasing hormone (TRH), which accelerates the secretion of TSH ( 28 ). Increased serum TSH can then act on TSH receptors in adipocytes to inhibit adipose triglyceride lipase, which in turn causes increased storage of triglycerides and an increase in adipocyte size, ultimately leading to overweight or obesity ( 29 ). Excess adipose tissue, especially large abdominal accumulations of dysfunctional fat, in turn increases triglyceride and LDL-C production, ultimately triggering insulin resistance and glucose dysregulation ( 30 , 31 ); thus, elevated TSH, TG, and LDL-C may trigger elevated fasting glucose in overweight/obese FEDN MDD patients.…”

Dorsoventral Arrangement of Lateral Hypothalamus Populations in the Mouse Hypothalamus: a Prosomeric Genoarchitectonic Analysis

“…Moreover, they co-express the genes Cartpt , Gal , Nts , and Tac2 encoding respectively the neuropeptides cocaine- and amphetamine-regulated transcript, galanin, neurotensin, and tachykinin [ 52 , 53 ]. Dlk1 is also expressed in LH4 cells; this gene encodes the delta-like non-canonical notch ligand 1, a protein implicated in cell proliferation or differentiation depending on the local context, which is also involved in hormone-producing pituitary cells [ 128 – 134 ]. These cell phenotypes match with two GABAergic clusters (1 and 3) identified by Mickelsen et al [ 42 ]; cluster 3 is characterized by co-expression of Cartpt and Nts , and cluster 1 contains cells expressing Nts , Gal , and Dlk1 transcripts ([ 42 ]; their Fig.…”

Prevalence and correlates of subclinical hypothyroidism in young first-episode drug-naïve major depression patients with high BMI

“…On the other hand, TSH can also stimulate leptin secretion by acting directly on adipocytes [38] . In summary, the interconnection between the thyroid axis and leptin in patients with FEND MDD may be a potential mechanism for the increase in TSH in patients with high BMI, and more investigations with larger samples are still needed to demonstrate this [34,39] .…”

“…First, one of the important mechanisms of MDD is a decrease in the concentration of 5hydroxytryptamine in the brain, which can lead to an increase in the concentration of thyroid stimulating hormones and thus accelerate TSH secretion [33] . An increase in serum TSH may trigger a sustained increase in triglyceride stores by inhibiting triglyceride lipase, leading to an increase in fat cells and leading to obesity [34,35] . Secondly, on the one hand, the excess fat leads to increased production of leptin, which stimulates TSH production via the hypothalamic pituitary axis [36,37] .…”