Obesity-associated extracellular mtDNA activates central TGF{beta} pathway to cause blood pressure increase
In conclusion, circulating mtDNA in the brain employs neural TGFβ pathway to mediate a central inflammatory mechanism of obesity-related hypertension. (Source: AJP: Endocrinology and Metabolism)
Source: AJP: Endocrinology and Metabolism - March 1, 2017 Category: Endocrinology Authors: Ale, A., Zhang, Y., Han, C., Cai, D. Tags: Research Article Source Type: research
Myostatin propeptide mutation of the hypermuscular Compact mice decreases the formation of myostatin and improves insulin sensitivity
In this study, by using mice strains carrying mutant or wild-type myostatin alleles with the Compact genetic background and nonmutant myostatin with the wild-type background, we studied separately the effect of the Mstn(Cmpt-dl1Abc) mutation or the Compact genetic background on morphology, metabolism, and signaling. We show that both the Compact myostatin mutation and Compact genetic background account for determination of skeletal muscle size. Despite the increased musculature of Compacts, the absolute size of heart and kidney is not influenced by myostatin mutation; however, the Compact genetic background increases them....
Source: AJP: Endocrinology and Metabolism - February 28, 2017 Category: Endocrinology Authors: Kocsis, T., Trencsenyi, G., Szabo, K., Baan, J. A., Muller, G., Mendler, L., Garai, I., Reinauer, H., Deak, F., Dux, L., Keller-Pinter, A. Tags: Research Article Source Type: research
Loss of glutaredoxin 3 impedes mammary lobuloalveolar development during pregnancy and lactation
Mammalian glutaredoxin 3 (Grx3) has been shown to be important for regulating cellular redox homeostasis in the cell. Our previous studies indicate that Grx3 is significantly overexpressed in various human cancers including breast cancer and demonstrate that Grx3 controls cancer cell growth and invasion by regulating reactive oxygen species (ROS) and NF-B signaling pathways. However, it remains to be determined whether Grx3 is required for normal mammary gland development and how it contributes to epithelial cell proliferation and differentiation in vivo. In the present study, we examined Grx3 expression in different cell ...
Source: AJP: Endocrinology and Metabolism - February 28, 2017 Category: Endocrinology Authors: Pham, K., Dong, J., Jiang, X., Qu, Y., Yu, H., Yang, Y., Olea, W., Marini, J. C., Chan, L., Wang, J., Wehrens, X. H. T., Cui, X., Li, Y., Hadsell, D. L., Cheng, N. Tags: Research Article Source Type: research
Acute and chronic hyperglycemic effects of vasopressin in normal rats: involvement of V1A receptors
Recent epidemiological studies have revealed novel relationships between low water intake or high vasopressin (AVP) and the risk of hyperglycemia and diabetes. AVP V1A and V1B receptors (R) are expressed in the liver and pancreatic islets, respectively. The present study was designed to determine the impact of different levels of circulating AVP on glucose homeostasis in normal Sprague-Dawley rats, as well as the respective roles of V1AR and V1BR. We showed that acute injection of AVP induces a dose-dependent increase in glycemia. Pretreatment with a selective V1AR antagonist, but not a V1BR antagonist, dose-dependently pr...
Source: AJP: Endocrinology and Metabolism - February 28, 2017 Category: Endocrinology Authors: Taveau, C., Chollet, C., Bichet, D. G., Velho, G., Guillon, G., Corbani, M., Roussel, R., Bankir, L., Melander, O., Bouby, N. Tags: Research Article Source Type: research
Effects of paternal obesity on growth and adiposity of male rat offspring
Emerging evidence suggests that paternal obesity plays an important role in offspring health. Our previous work using a rodent model of diet-induced paternal obesity showed that female offspring from high-fat diet (HFD)-fed fathers develop glucose intolerance due to impairment of pancreatic insulin secretion. Here, we focused on the health outcomes of male offspring from HFD-fed fathers. Male Sprague-Dawley rats (3 wk old) were fed control (CD-F0) or HFD (HFD-F0) for 12 wk before mating with control-fed females. Male offspring were fed control diets for up to 8 wk or 6 mo. Although male offspring from HFD-F0 did not develo...
Source: AJP: Endocrinology and Metabolism - February 7, 2017 Category: Endocrinology Authors: Lecomte, V., Maloney, C. A., Wang, K. W., Morris, M. J. Tags: Research Article Source Type: research
Reduced islet function contributes to impaired glucose homeostasis in fructose-fed mice
Increased sugar consumption, particularly fructose, in the form of sweetened beverages and sweeteners in our diet adversely affects metabolic health. Because these effects are associated with features of the metabolic syndrome in humans, the direct effect of fructose on pancreatic islet function is unknown. Therefore, we examined the islet phenotype of mice fed excess fructose. Fructose-fed mice exhibited fasting hyperglycemia and glucose intolerance but not hyperinsulinemia, dyslipidemia, or hyperuricemia. Islet function was impaired, with decreased glucose-stimulated insulin secretion and increased glucagon secretion and...
Source: AJP: Endocrinology and Metabolism - February 7, 2017 Category: Endocrinology Authors: Asghar, Z. A., Cusumano, A., Yan, Z., Remedi, M. S., Moley, K. H. Tags: Research Article Source Type: research
Postnatal treatment with metyrapone attenuates the effects of diet-induced obesity in female rats exposed to early-life stress
This study tested the hypothesis that female rat pups exposed to maternal separation (MatSep), a model of early-life stress, display an exacerbated response to diet-induced obesity compared with male rats. Also, we tested whether the postnatal treatment with metyrapone (MTP), a corticosterone synthase inhibitor, would attenuate this phenotype. MatSep was performed in WKY offspring by separation from the dam (3 h/day, postnatal days 2–14). Upon weaning, male and female rats were placed on a normal (ND; 18% kcal fat) or high-fat diet (HFD; 60% kcal fat). Nondisturbed littermates served as controls. In male rats, no die...
Source: AJP: Endocrinology and Metabolism - January 31, 2017 Category: Endocrinology Authors: Murphy, M. O., Herald, J. B., Wills, C. T., Unfried, S. G., Cohn, D. M., Loria, A. S. Tags: Research Article Source Type: research
Long-term high-fat diet induces hippocampal microvascular insulin resistance and cognitive dysfunction
Insulin action on hippocampus improves cognitive function, and obesity and type 2 diabetes are associated with decreased cognitive function. Cerebral microvasculature plays a critical role in maintaining cerebral vitality and function by supplying nutrients, oxygen, and hormones such as insulin to cerebral parenchyma, including hippocampus. In skeletal muscle, insulin actively regulates microvascular opening and closure, and this action is impaired in the insulin-resistant states. To examine insulin’s action on hippocampal microvasculature and parenchyma and the impact of diet-induced obesity, we determined cognitive...
Source: AJP: Endocrinology and Metabolism - January 31, 2017 Category: Endocrinology Authors: Fu, Z., Wu, J., Nesil, T., Li, M. D., Aylor, K. W., Liu, Z. Tags: Research Article Source Type: research
UCP1 inhibition in Cidea-overexpressing mice is physiologically counteracted by brown adipose tissue hyperrecruitment
Cidea is a gene highly expressed in thermogenesis-competent (UCP1-containing) adipose cells, both brown and brite/beige. Here, we initially demonstrate a remarkable adipose-depot specific regulation of Cidea expression. In classical brown fat, Cidea mRNA is expressed continuously and invariably, irrespective of tissue recruitment. However, Cidea protein levels are regulated posttranscriptionally, being conspicuously induced in the thermogenically recruited state. In contrast, in brite fat, Cidea protein levels are regulated at the transcriptional level, and Cidea mRNA and protein levels are proportional to tissue "britenes...
Source: AJP: Endocrinology and Metabolism - January 10, 2017 Category: Endocrinology Authors: Fischer, A. W., Shabalina, I. G., Mattsson, C. L., Abreu-Vieira, G., Cannon, B., Nedergaard, J., Petrovic, N. Tags: Research Article Source Type: research
High-fat diet-induced obesity regulates MMP3 to modulate depot- and sex-dependent adipose expansion in C57BL/6J mice
Increased adipocyte size is hypothesized to signal the recruitment of adipose progenitor cells (APCs) to expand tissue storage capacity. To investigate depot and sex differences in adipose growth, male and female C57BL/6J mice (10 wk-old) were challenged with high-fat (HF) or low-fat (LF) diets (D) for 14 wk. The HFD increased gonadal (GON) depot weight by adipocyte hypertrophy and hyperplasia in females but hypertrophy alone in males. In both sexes, inguinal (ING) adipocytes were smaller than GON, and depot expansion was due to hypertrophy. Matrix metalloproteinase 3 (Mmp3), an antiadipogenic factor, and its inhibitor Tim...
Source: AJP: Endocrinology and Metabolism - January 10, 2017 Category: Endocrinology Authors: Wu, Y., Lee, M.-J., Ido, Y., Fried, S. K. Tags: Research Article Source Type: research
Glucosamine induces ER stress by disrupting lipid-linked oligosaccharide biosynthesis and N-linked protein glycosylation
In this study, we investigate the potential relationship between the effects of glucosamine on lipid-linked oligosaccharide (LLO) biosynthesis, N-linked glycosylation, and ER homeostasis. Mouse embryonic fibroblasts (MEFs) were cultured in the presence of 0–5 mM glucosamine for up to 18 h, and LLO biosynthesis was monitored by fluorescence-assisted carbohydrate electrophoresis. ER stress was determined by quantification of unfolded protein response (UPR) gene expression. We found that exposure of MEFs to ≥1 mM glucosamine significantly impaired the biosynthesis of mature (Glc3Man9GlcNAc2) LLOs before the activatio...
Source: AJP: Endocrinology and Metabolism - December 31, 2016 Category: Endocrinology Authors: Beriault, D. R., Dang, V. T., Zhong, L. H., Petlura, C. I., McAlpine, C. S., Shi, Y., Werstuck, G. H. Tags: Research Article Source Type: research
Dietary gossypol suppressed postprandial TOR signaling and elevated ER stress pathways in turbot (Scophthalmus maximus L.)
Gossypol is known to be a polyphenolic compound toxic to animals. However, its molecular targets are far from fully characterized. To evaluate the physiological and molecular effects of gossypol, we chose turbot (Scophthalmus maximus L.), a carnivorous fish, as our model species. Juvenile turbots (7.83 ± 0.02 g) were fed diets containing gradient levels of gossypol at 0 (G0), 600 (G1), and 1,200 (G2) mg/kg diets for 11 wk. After the feeding trial, fish growth, body protein, and fat contents were significantly reduced in the G2 group compared with those of the G0 group (P < 0.05). Gossypol had little impact on dig...
Source: AJP: Endocrinology and Metabolism - December 31, 2016 Category: Endocrinology Authors: Bian, F., Jiang, H., Man, M., Mai, K., Zhou, H., Xu, W., He, G. Tags: Research Article Source Type: research
Citrulline directly modulates muscle protein synthesis via the PI3K/MAPK/4E-BP1 pathway in a malnourished state: evidence from in vivo, ex vivo, and in vitro studies
Citrulline (CIT) is an endogenous amino acid produced by the intestine. Recent literature has consistently shown CIT to be an activator of muscle protein synthesis (MPS). However, the underlying mechanism is still unknown. Our working hypothesis was that CIT might regulate muscle homeostasis directly through the mTORC1/PI3K/MAPK pathways. Because CIT undergoes both interorgan and intraorgan trafficking and metabolism, we combined three approaches: in vivo, ex vivo, and in vitro. Using a model of malnourished aged rats, CIT supplementation activated the phosphorylation of S6K1 and 4E-BP1 in muscle. Interestingly, the increa...
Source: AJP: Endocrinology and Metabolism - December 31, 2016 Category: Endocrinology Authors: Le Plenier, S., Goron, A., Sotiropoulos, A., Archambault, E., Guihenneuc, C., Walrand, S., Salles, J., Jourdan, M., Neveux, N., Cynober, L., Moinard, C. Tags: Research Article Source Type: research
Evaluation of CSF and plasma biomarkers of brain melanocortin activity in response to caloric restriction in humans
The objective of this study was to measure the POMC prohormone and its processed peptide, β-endorphin (β-EP), in cerebrospinal fluid (CSF) and AgRP in CSF and plasma after calorie restriction to validate their utility as biomarkers of brain melanocortin activity. CSF and plasma were obtained from 10 lean and obese subjects after fasting (40 h) and refeeding (24 h), and from 8 obese subjects before and after 6 wk of dieting (800 kcal/day) to assess changes in neuropeptide and hormone levels. After fasting, plasma leptin decreased to 35%, and AgRP increased to 153% of baseline. During refeeding, AgRP declined as le...
Source: AJP: Endocrinology and Metabolism - December 31, 2016 Category: Endocrinology Authors: Page-Wilson, G., Nguyen, K. T., Atalayer, D., Meece, K., Bainbridge, H. A., Korner, J., Gordon, R. J., Panigrahi, S. K., White, A., Smiley, R., Wardlaw, S. L. Tags: Research Article Source Type: research
Kupffer cells facilitate the acute effects of leptin on hepatic lipid metabolism
Leptin has potent effects on lipid metabolism in a number of peripheral tissues. In liver, an acute leptin infusion (~120 min) stimulates hepatic fatty acid oxidation (~30%) and reduces triglycerides (TG, ~40%), effects that are dependent on phosphoinositol-3-kinase (PI3K) activity. In the current study we addressed the hypothesis that leptin actions on liver-resident immune cells are required for these metabolic effects. Myeloid cell-specific deletion of the leptin receptor (ObR) in mice or depletion of liver Kupffer cells (KC) in rats in vivo prevented the acute effects of leptin on liver lipid metabolism, while the meta...
Source: AJP: Endocrinology and Metabolism - December 31, 2016 Category: Endocrinology Authors: Metlakunta, A., Huang, W., Stefanovic-Racic, M., Dedousis, N., Sipula, I., ODoherty, R. M. Tags: Research Article Source Type: research
