Metabolic and melanocortin gene expression alterations in male offspring of obese mice

Gout, Johann; Sarafian, Delphine; Mutel, E.; Vigier, Michèle; Rajas, Fabienne; Mithieux, Gilles; Bégeot, Martine; Naville, Danielle

doi:10.1016/j.mce.2010.01.021

Cited by 16 publications

(18 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Accordingly, the decrease in serum concentrations of leptin in arthritic rats can be responsible for the increased expression of anorexigenic hypothalamic peptides. In this sense, the opposite response has been reported in obese rats, where food intake and circulating leptin is increased although POMC is increased and NPY is reduced (14,20).…”

Section: Discussionmentioning

confidence: 88%

Systemic α-melanocyte-stimulating hormone administration decreases arthritis-induced anorexia and muscle wasting

Gómez-SanMiguel

Martín

Nieto-Bona

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

Rheumatoid cachexia is associated with rheumatoid arthritis and it increases mortality and morbidity. Adjuvant-induced arthritis is an experimental model of rheumatoid arthritis that causes anorexia and muscle wasting. α-Melanocyte-stimulating hormone (α-MSH) has anti-inflammatory actions, and it is able to decrease inflammation in several inflammatory diseases including experimental arthritis. In this study we tested whether systemic α-MSH treatment is able to ameliorate cachexia in arthritic rats. On day 8 after adjuvant injection control and arthritic rats were treated with α-MSH (50 μg/rat ip) twice a day, until day 16 when all rats were euthanized. Arthritis decreased food intake, but it increased hypothalamic expression of neuropeptide Y (NPY) and Agouti-related peptides (AgRP) as well as interleukin-1β (IL-1β) and cyclooxygenase-2 (COX-2) mRNA. In arthritic rats, α-MSH decreased the external signs of arthritis and increased food intake (P < 0.01). In addition, α-MSH decreased hypothalamic expression of IL-1β, COX-2, proopiomelanocortin, and prohormone-converting (PC) enzymes PC1/3 and PC2 mRNA in arthritic rats. In control rats, α-MSH did not modify food intake or hypothalamic expression of aforementioned mRNA. α-MSH prevented arthritis-induced increase in gastrocnemius COX-2, muscle-specific RING-finger protein-1 (MuRF1), and atrogin-1 expression, and it increased fast myofiber size. In conclusion our data show that in arthritic rats peripheral α-MSH treatment has an anti-cachectic action increasing food intake and decreasing muscle wasting.

show abstract

Section: Discussionmentioning

confidence: 88%

Systemic α-melanocyte-stimulating hormone administration decreases arthritis-induced anorexia and muscle wasting

Gómez-SanMiguel

Martín

Nieto-Bona

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

show abstract

“…Although leptin increases hypothalamic Pomc mRNA and reduces Agrp mRNA in adult rodents (43,63), the expression of these genes is not altered in neonatal mice that are chronically treated with leptin (1), a finding that is consistent with the results of the current experiment. In other studies in mice and rats, maternal HF diet consumption has been linked to decreased (44), increased (25,31), or unchanged (25) hypothalamic Pomc and Agrp gene expression in late embryonic (E19.5-E21) or neonatal (P1) offspring. Differences in the timing, duration, and fatty acid composition of the HF diets in the different studies might explain these disparate outcomes.…”

Section: Discussionmentioning

confidence: 90%

“…The programming effects of increased maternal fat consumption during pregnancy and lactation are typically exacerbated when the offspring are also fed an energy-rich diet postweaning, demonstrating that metabolic adaptations that are programmed during prenatal development can be modified by postnatal growth and nutrition (11,20,36,56). In contrast, other investigators have restricted their nutritional insult to the intrauterine environment by studying the offspring of high-fat (HF) diet-fed females during late fetal development or immediately after birth (25,31,37,44,56). For example, our laboratory and others have demonstrated that early third-trimester, nonhuman primate fetuses exhibit systemic inflammation, hepatic steatosis, increased hepatic oxidative stress with concurrent apoptotic cell death, and altered hypothalamic development in response to maternal consumption of a HF diet (26,27,42).…”

mentioning

confidence: 99%

Increased maternal fat consumption during pregnancy alters body composition in neonatal mice

Krasnow

Nguyen

Marks

2011

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

Krasnow SM, Nguyen MT, Marks DL. Increased maternal fat consumption during pregnancy alters body composition in neonatal mice. Am J Physiol Endocrinol Metab 301: E1243-E1253, 2011. First published September 6, 2011 doi:10.1152/ajpendo.00261.2011Maternal overnutrition prior to and during gestation causes pronounced metabolic dysfunction in the adult offspring. However, less is known about metabolic adaptations in the offspring that occur independently of postnatal growth and nutrition. Therefore, we evaluated the impact of excess maternal dietary lipid intake on the in utero programming of body composition, hepatic function, and hypothalamic development in newborn (P0) offspring. Female mice were fed a low-fat (LF) or high-fat (HF) diet and were mated after 4, 12, and 23 wk. A subset of the obese HF dams was switched to the LF diet during the second (DR2) or third (DR3) pregnancies. The HF offspring accrued more fat mass than the LF pups, regardless of duration of maternal HF diet consumption or prepregnancy maternal adiposity. Increased neonatal adiposity was not observed in the DR3 pups. Liver weights were reduced in the HF offspring but not in the DR2 or DR3 pups. Offspring hepatic triglyceride content was reduced in the HF pups, but hepatic inflammation and expression of lipid metabolism genes were largely unaffected by maternal diet. Maternal diet did not alter the hypothalamic expression of orexigenic and anorexigenic neuropeptides in the offspring. Thus, the intrauterine programming of increased neonatal adiposity and reduced liver size by maternal overnutrition is evident in mice at birth and occurs prior to the development of maternal obesity. These observations demonstrate that dietary intervention during pregnancy minimizes the deleterious effects of maternal obesity on offspring body composition, potentially reducing the offsprings' risk of developing obesity and related diseases later in life. metabolic programming; liver; hypothalamus; inflammation; obesity THE GLOBAL PREVALENCE OF OBESITY has reached epidemic proportions in recent years, not only threatening the health and well-being of affected individuals but also imposing a considerable burden on the economic and health care systems of developed and developing nations (33). In the US, the prevalence of obesity has more than doubled in adults and more than tripled in children and adolescents since the 1970s. According to estimates from the 2007-2008 National Health and Nutrition Examination Survey, 33.8% of adults and 16.9% of children aged 2-19 are obese, and 9.5% of infants and toddlers are at or above the 95th percentile of the weight-for-length growth charts (23,24,45,46). Obese individuals have an increased risk of developing type 2 diabetes mellitus, hypertension, dyslipidemia, and nonalcoholic fatty liver disease. Once restricted to adults, these metabolic diseases and conditions are now being diagnosed in children and adolescents at alarming rates, mirroring the rising rates of juvenile obesity (34,39,47,52,55).The etiology of obesity is...

show abstract

“…The MCS stands as a likely candidate to mediate the behavioral, hormonal and metabolic consequences of nutritional manipulation [24]. However, in a previous study pertaining to the regulation of the expression of the hypothalamic MCS by a high fat-diet, we unexpectedly observed an increase in the POMC to AgRP ratio, whilst mice fed this type of regimen exhibited hyperphagia and obesity [25]. This has suggested that the MCS might combat, rather than mediate, the changes in food intake induced by the diet.…”

Section: Introductionmentioning

confidence: 62%

Role of Hypothalamic Melanocortin System in Adaptation of Food Intake to Food Protein Increase in Mice

et al. 2011

Self Cite

View full text Add to dashboard Cite

The hypothalamic melanocortin system—the melanocortin receptor of type 4 (MC4R) and its ligands: α-melanin-stimulating hormone (α-MSH, agonist, inducing hypophagia), and agouti-related protein (AgRP, antagonist, inducing hyperphagia)—is considered to play a central role in the control of food intake. We tested its implication in the mediation of the hunger-curbing effects of protein-enriched diets (PED) in mice. Whereas there was a 20% decrease in food intake in mice fed on the PED, compared to mice fed on an isocaloric starch-enriched diet, there was a paradoxical decrease in expression of the hypothalamic proopiomelanocortin gene, precursor of α-MSH, and increase in expression of the gene encoding AgRP. The hypophagia effect of PED took place in mice with invalidation of either MC4R or POMC, and was even strengthened in mice with ablation of the AgRP-expressing neurons. These data strongly suggest that the hypothalamic melanocortin system does not mediate the hunger-curbing effects induced by changes in the macronutrient composition of food. Rather, the role of this system might be to defend the body against the variations in food intake generated by the nutritional environment.

show abstract

Metabolic and melanocortin gene expression alterations in male offspring of obese mice

Cited by 16 publications

References 55 publications

Systemic α-melanocyte-stimulating hormone administration decreases arthritis-induced anorexia and muscle wasting

Systemic α-melanocyte-stimulating hormone administration decreases arthritis-induced anorexia and muscle wasting

Increased maternal fat consumption during pregnancy alters body composition in neonatal mice

Role of Hypothalamic Melanocortin System in Adaptation of Food Intake to Food Protein Increase in Mice

Contact Info

Product

Resources

About