Agouti-Related Protein Antagonizes Glucocorticoid Production Induced through Melanocortin 4 Receptor Activation in Bovine Adrenal Cells: A Possible Autocrine Control

Doghman, Mabrouka; Delagrange, Philippe; Blondet, Antonine; Berthelon, M.; Durand, Philippe; Naville, Danielle; Bégeot, Martine

doi:10.1210/en.2003-0605

Cited by 35 publications

(19 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We also observed a fasting-induced up-regulation of MRAP mRNA in WT mice that did not exist in MC3-R −/− mice. Finally, we monitored AgRP mRNA, because adrenal AgRP expression is up-regulated during a fast and is thought to play a role in controlling corticosterone release (43,44). Similar to both MC2-R and MRAP, AgRP mRNA was up-regulated by fasting in WT mice but not in MC3-R −/− mice.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Melanocortin-3 receptor regulates the normal fasting response

Renquist

Murphy

Larson

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The melanocortin-3 receptor-deficient (MC3-R −/− ) mouse exhibits mild obesity without hyperphagia or hypometabolism. MC3-R deletion is reported to increase adiposity, reduce lean mass and white adipose tissue inflammation, and increase sensitivity to salt-induced hypertension. We show here that the MC3-R −/− mouse exhibits defective fasting-induced white adipose tissue lipolysis, fasting-induced liver triglyceride accumulation, fasting-induced refeeding, and fasting-induced regulation of the adipostatic and hypothalamic-adrenal-pituitary axes. Close examination of the hypothalamic-pituitary-adrenal axis showed that MC3-R −/− mice exhibit elevated nadir corticosterone as well as a blunted fasting-induced activation of the axis. The previously described phenotypes of this animal and the reduced bone density reported here parallel those of Cushing syndrome. Thus, MC3-R is required for communicating nutritional status to both central and peripheral tissues involved in nutrient partitioning, and this defect explains much of the metabolic phenotype in the model. energy homeostasis | nonesterified fatty acid | corticotrophin-releasing hormone | hormone-sensitive lipase R esearch on the central melanocortin system has focused on the role of the melanocortin-4 receptor (MC4-R) in energy homeostasis, particularly as a result of the hyperphagic obesity syndrome found in both mice and humans with mutations in this receptor (1-3). A large body of work has demonstrated that circuitry regulated by the MC4-R is essential for much of leptin action and coordinates energy intake with energy expenditure to maintain long-term energy homeostasis (4). In contrast, the melanocortin-3 receptor (MC3-R), expressed in ∼35 different nuclei in the CNS with a pattern distinct from that of the MC4-R

show abstract

Section: Discussionmentioning

confidence: 99%

“…Thus, a non-CRH-mediated mechanism leading to elevated basal corticosterone in the MC3-R −/− is possible also. In fact, it is possible that MC3-R deletion from the adrenal gland results in hypercorticosteronemia by eliminating the ability of AgRP to induce its paracrine inhibitory effects on corticosterone (20,44).…”

Section: Discussionmentioning

confidence: 99%

Melanocortin-3 receptor regulates the normal fasting response

Renquist

Murphy

Larson

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…From the lack of MC2R expression and the stable MC1R expression they concluded that melanocortins regulate cell proliferation and inflammatory processes rather than lipolysis in human adipose tissue. Although several groups detected different members of the MCR family in a variety of bovine tissues, no data exist for adipose tissue so far [29], [58]–[60]. In this context we targeted all MCR in bovine SCF.…”

Section: Discussionmentioning

confidence: 99%

Agouti Revisited: Transcript Quantification of the ASIP Gene in Bovine Tissues Related to Protein Expression and Localization

et al. 2012

View full text Add to dashboard Cite

Beside its role in melanogenesis, the agouti signaling protein (ASIP) has been related to obesity. The potentially crucial role in adipocyte development makes it a tempting candidate for economic relevant, fat related traits in farm animals. The objective of our study was to characterize the mRNA expression of different ASIP transcripts and of putative targets in different bovine tissues, as well as to study consequences on protein abundance and localization. ASIP mRNA abundance was determined by RT-qPCR in adipose and further tissues of cattle representing different breeds and crosses. ASIP mRNA was up-regulated more than 9-fold in intramuscular fat of Japanese Black cattle compared to Holstein (p<0.001). Further analyses revealed that a transposon-derived transcript was solely responsible for the increased ASIP mRNA abundance. This transcript was observed in single individuals of different breeds indicating a wide spread occurrence of this insertion at the ASIP locus in cattle. The protein was detected in different adipose tissues, skin, lung and liver, but not in skeletal muscle by Western blot with a bovine-specific ASIP antibody. However, the protein abundance was not related to the observed ASIP mRNA over-expression. Immuno-histochemical analyses revealed a putative nuclear localization of ASIP additionally to the expected cytosolic signal in different cell types. The expression of melanocortin receptors (MCR) 1 to 5 as potential targets for ASIP was analyzed by RT-PCR in subcutaneous fat. Only MC1R and MC4R were detected indicating a similar receptor expression like in human adipose tissue. Our results provide evidence for a widespread expression of ASIP in bovine tissues at mRNA and, for the first time, at protein level. ASIP protein is detectable in adipocytes as well as in further cells of adipose tissue. We generated a basis for a more detailed investigation of ASIP function in peripheral tissues of various mammalian species.

show abstract

“…Both MC3R and MC4R are expressed in rat adrenal gland and can bind ACTH with the same affinity as ␣-MSH (58,177). MC4R is also expressed in human adrenal tissue, whereas MC3R expression has been detected in the human adrenocortical cell line H295R (60). AGRP is present in bovine adrenocortical cells and inhibits both acute and long-term Nle4,D-Phe7 (NDP)-␣-MSH-and ACTH-induced cortisol production by antagonistic action toward MC4R, in addition to inhibiting ACTH-induced longterm cortisol production, in a biphasic manner independent of MC2R (59 -61).…”

Section: Glucocorticoids Play An Important Role In Insulin Resistancementioning

confidence: 99%

Adrenocortical dysregulation as a major player in insulin resistance and onset of obesity

Roberge¹,

Carpentier²,

Langlois³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

The aim of this review is to explore the dysregulation of adrenocortical secretions as a major contributor in the development of obesity and insulin resistance. Disturbance of adipose tissue physiology is one of the primary events in the development of pathologies associated with the metabolic syndrome, such as obesity and type 2 diabetes. Several studies indicate that alterations in metabolism of glucocorticoids (GC) and androgens, as well as aldosterone in excess, are involved in the emergence of metabolic syndrome. Cross talk among adipose tissue, the hypothalamo-pituitary complex, and adrenal gland activity plays a major role in the control of food intake, glucose metabolism, lipid storage, and energy balance. Perturbation of this cross talk induces alterations in the regulatory mechanisms of adrenocortical steroid synthesis, secretion, degradation, and/or recycling, at the level of the zonae glomerulosa (aldosterone), fasciculata (GC and GC metabolites), and reticularis (androgens and androgen precursors DHEA and DHEAS). As a whole, these adrenocortical perturbations contribute to the development of metabolic syndrome at both the paracrine and systemic level by favoring the physiological dysregulation of organs responsive to aldosterone, GC, and/or androgens, including adipose tissue. adrenal gland; adipocytes; angiotensin II; adrenocorticotropic hormone; adrenal steroids INSULIN RESISTANCE (IR), which is characterized by an insufficiency in insulin action, is associated with pathologies related to the metabolic syndrome, such as central obesity, hypertension, and dyslipidimia, and leads to increased risk of type 2 diabetes and cardiovascular diseases. Common forms of obesity and type 2 diabetes are polygenic diseases, resulting from complex interactions between genetic predispositions and environmental factors (18, 42), with particular importance of dietary fat intake (114,146). Current data converge to indicate that dysregulation in adipose tissue physiology is one of the primary events in the development of insulin resistance (52, 109, 111), although other insulin-and glucocorticoid-responsive organs such as skeletal muscles and liver may also play a primary role (144, 168). Several publications and reviews also point to glucocorticoids (GC) (151,190) and the renin-angiotensin system (RAS) as key players in controlling adipose tissue physiology (187). However, several reports indicate cross-talk relationships among the hypothalamo-pituitary-adrenal (HPA) axis, the melanocortin pathways, and the adipose tissue. Combination of certain gene variants with environmental factors, such as overheating, sedentarity, and chronic stress, appears to alter this cross talk, hence inducing perturbations in the regulatory mechanisms of adrenocortical steroid synthesis, secretion, degradation, and/or recycling. The aim of the present review is to explore the dysregulation of adrenocortical secretions as a major contributor in the development of obesity and insulin resistance. Structure and Functions of the Adrenal Cortex...

show abstract

Agouti-Related Protein Antagonizes Glucocorticoid Production Induced through Melanocortin 4 Receptor Activation in Bovine Adrenal Cells: A Possible Autocrine Control

Cited by 35 publications

References 39 publications

Melanocortin-3 receptor regulates the normal fasting response

Melanocortin-3 receptor regulates the normal fasting response

Agouti Revisited: Transcript Quantification of the ASIP Gene in Bovine Tissues Related to Protein Expression and Localization

Adrenocortical dysregulation as a major player in insulin resistance and onset of obesity

Contact Info

Product

Resources

About