"Calories in, calories out" and macronutrient intake: the hope, hype, and science of calories
One of the central tenets in obesity prevention and management is caloric restriction. This perspective presents salient features of how calories and energy balance matter, also called the "calories in, calories out" paradigm. Determinants of energy balance and relationships to dietary macronutrient content are reviewed. The rationale and features of the carbohydrate-insulin hypothesis postulate that carbohydrate restriction confers a metabolic advantage. According to this model, a large amount of fat intake is enabled without weight gain. Evidence concerning this possibility is detailed. The relationship and application o...
Source: AJP: Endocrinology and Metabolism - November 29, 2017 Category: Endocrinology Authors: Howell, S., Kones, R. Tags: Perspective Source Type: research
Optimization of tolerability and efficacy of the novel dual amylin and calcitonin receptor agonist KBP-089 through dose escalation and combination with a GLP-1 analog
In conclusion, DACRAs act complementarily with GLP-1 on food intake and body weight. Furthermore, on escalation, KBP-089 was well tolerated and induced and sustained a significant weight loss and a reduction in AT in lean and HFD rats, underscoring the potential of KBP-089 as an anti-obesity agent. (Source: AJP: Endocrinology and Metabolism)
Source: AJP: Endocrinology and Metabolism - November 29, 2017 Category: Endocrinology Authors: Gydesen, S., Andreassen, K. V., Hjuler, S. T., Hellgren, L. I., Karsdal, M. A., Henriksen, K. Tags: Research Article Source Type: research
Dihydrocapsiate improved age-associated impairments in mice by increasing energy expenditure
In this study, we investigated whether DCT supplementation in aged mice improves age-associated impairments. We obtained 5-wk-old and 1-yr-old male C57BL/6J mice and randomly assigned the aged mice to two groups, resulting in a total of three groups: 1) young mice, 2) old mice, and 3) old mice supplemented with 0.3% DCT. After 12 wk of supplementation, blood and tissue samples were collected and analyzed. DCT significantly suppressed age-associated fat accumulation, adipocyte hypertrophy, and liver steatosis. In addition, the DCT treatment dramatically suppressed age-associated increases in hepatic inflammation, immune cel...
Source: AJP: Endocrinology and Metabolism - November 29, 2017 Category: Endocrinology Authors: Ohyama, K., Suzuki, K. Tags: Research Article Source Type: research
Glucose oxidation positively regulates glucose uptake and improves cardiac function recovery after myocardial reperfusion
Myocardial reperfusion decreases glucose oxidation and uncouples glucose oxidation from glycolysis. Therapies that increase glucose oxidation lessen myocardial ischemia-reperfusion (I/R) injury. However, the regulation of glucose uptake during reperfusion remains poorly understood. We found that glucose uptake was remarkably diminished in the myocardium following reperfusion in Sprague-Dawley rats as detected by 18F–labeled and fluorescent-labeled glucose analogs, even though GLUT1 was upregulated by threefold and GLUT4 translocation remained unchanged compared with those of sham-treated rats. The decreased glucose u...
Source: AJP: Endocrinology and Metabolism - November 29, 2017 Category: Endocrinology Authors: Li, T., Xu, J., Qin, X., Hou, Z., Guo, Y., Liu, Z., Wu, J., Zheng, H., Zhang, X., Gao, F. Tags: Research Article Source Type: research
Dapagliflozin slows the progression of the renal and liver fibrosis associated with type 2 diabetes
This study sought to address these questions by treating 18-wk-old uninephrectomized db/db mice with the selective SGLT2 inhibitor dapagliflozin. Untreated db/db mice developed progressive albuminuria, glomerular mesangial matrix expansion, and fatty liver associated with increased renal expression of TGFβ1, PAI-1, type IV collagen and fibronectin, and liver deposition of fibronectin, type I and III collagen, and laminin. Treatment with dapagliflozin (1 mg·kg–1·day–1) via gel diet from 18 to 22 wk of age not only reduced blood glucose (371.14 ± 55.02 mg/dl in treated db/db vs. 573.53 &...
Source: AJP: Endocrinology and Metabolism - November 29, 2017 Category: Endocrinology Authors: Tang, L., Wu, Y., Tian, M., Sjöström, C. D., Johansson, U., Peng, X.-R., Smith, D. M., Huang, Y. Tags: Research Article Source Type: research
Long-term rates of mitochondrial protein synthesis are increased in mouse skeletal muscle with high-fat feeding regardless of insulin-sensitizing treatment
Skeletal muscle mitochondrial protein synthesis is regulated in part by insulin. The development of insulin resistance with diet-induced obesity may therefore contribute to impairments to protein synthesis and decreased mitochondrial respiration. Yet the impact of diet-induced obesity and insulin resistance on mitochondrial energetics is controversial, with reports varying from decreases to increases in mitochondrial respiration. We investigated the impact of changes in insulin sensitivity on long-term rates of mitochondrial protein synthesis as a mechanism for changes to mitochondrial respiration in skeletal muscle. Insul...
Source: AJP: Endocrinology and Metabolism - November 29, 2017 Category: Endocrinology Authors: Newsom, S. A., Miller, B. F., Hamilton, K. L., Ehrlicher, S. E., Stierwalt, H. D., Robinson, M. M. Tags: Research Article Source Type: research
Cross-sex testosterone therapy in ovariectomized mice: addition of low-dose estrogen preserves bone architecture
Cross-sex hormone therapy (XHT) is widely used by transgender people to alter secondary sex characteristics to match their desired gender presentation. Here, we investigate the long-term effects of XHT on bone health using a murine model. Female mice underwent ovariectomy at either 6 or 10 wk and began weekly testosterone or vehicle injections. Dual-energy X-ray absorptiometry (DXA) was performed (20 wk) to measure bone mineral density (BMD), and microcomputed tomography was performed to compare femoral cortical and trabecular bone architecture. The 6-wk testosterone group had comparable BMD with controls by DXA but reduce...
Source: AJP: Endocrinology and Metabolism - November 1, 2017 Category: Endocrinology Authors: Goetz, L. G., Mamillapalli, R., Devlin, M. J., Robbins, A. E., Majidi-Zolbin, M., Taylor, H. S. Tags: Research Article Source Type: research
Circulating sex steroids coregulate adipose tissue immune cell populations in healthy men
Male hypogonadism results in changes in body composition characterized by increases in fat mass. Resident immune cells influence energy metabolism in adipose tissue and could promote increased adiposity through paracrine effects. We hypothesized that manipulation of circulating sex steroid levels in healthy men would alter adipose tissue immune cell populations. Subjects (n = 44 men, 19–55 yr of age) received 4 wk of treatment with the gonadotropin-releasing hormone receptor antagonist acyline with daily administration of 1) placebo gel, 2) 1.25 g testosterone gel (1.62%), 3) 5 g testosterone gel, or 4) 5 g testoster...
Source: AJP: Endocrinology and Metabolism - November 1, 2017 Category: Endocrinology Authors: Rubinow, K. B., Chao, J. H., Hagman, D., Kratz, M., Van Yserloo, B., Gaikwad, N. W., Amory, J. K., Page, S. T. Tags: Research Article Source Type: research
Adaptive facultative diet-induced thermogenesis in wild-type but not in UCP1-ablated mice
The significance of diet-induced thermogenesis (DIT) for metabolic control is still debated. Although obesogenic diets recruit UCP1 and adrenergically inducible thermogenesis, and although the absence of UCP1 may promote the development of obesity, no actual UCP1-related thermogenesis identifiable as diet-induced thermogenesis has to date been unambiguously demonstrated. Examining mice living at thermoneutrality, we have identified a process of facultative (directly elicited by acute eating), adaptive (magnitude develops over weeks on an obesogenic diet), and fully UCP1-dependent thermogenesis. We found no evidence for UCP...
Source: AJP: Endocrinology and Metabolism - November 1, 2017 Category: Endocrinology Authors: von Essen, G., Lindsund, E., Cannon, B., Nedergaard, J. Tags: Research Article Source Type: research
Extraovarian gonadotropin negative feedback revealed by aromatase inhibition in female marmoset monkeys
Whereas the ovary produces the majority of estradiol (E2) in mature female primates, extraovarian sources contribute to E2 synthesis and action, including the brain E2-regulating hypothalamic gonadotropin-releasing hormone. In ovary-intact female rodent models, aromatase inhibition (AI) induces a polycystic ovary syndrome-like hypergonadotropic hyperandrogenism due to absent E2-mediated negative feedback. To examine the role of extraovarian E2 on nonhuman primate gonadotropin regulation, the present study uses letrozole to elicit AI in adult female marmoset monkeys. Sixteen female marmosets (Callithrix jacchus; >2 yr) w...
Source: AJP: Endocrinology and Metabolism - November 1, 2017 Category: Endocrinology Authors: Kraynak, M., Flowers, M. T., Shapiro, R. A., Kapoor, A., Levine, J. E., Abbott, D. H. Tags: Research Article Source Type: research
SIRT6 regulates metabolic homeostasis in skeletal muscle through activation of AMPK
Because of the mass and functions in metabolism, skeletal muscle is one of the major organs regulating whole body metabolic homeostasis. SIRT6, a histone deacetylase, has been shown to regulate metabolism in liver and brain; however, its specific role in skeletal muscle is undetermined. In the present study we explored physiological function of SIRT6 in muscle. We generated a muscle-specific SIRT6 knockout mouse model. The mice with SIRT6 deficiency in muscle displayed impaired glucose homeostasis and insulin sensitivity, attenuated whole body energy expenditure, and weakened exercise performance. Mechanistically, deletion...
Source: AJP: Endocrinology and Metabolism - October 9, 2017 Category: Endocrinology Authors: Cui, X., Yao, L., Yang, X., Gao, Y., Fang, F., Zhang, J., Wang, Q., Chang, Y. Tags: Research Article Source Type: research
Corrigendum
(Source: AJP: Endocrinology and Metabolism)
Source: AJP: Endocrinology and Metabolism - October 1, 2017 Category: Endocrinology Tags: Corrigendum Source Type: research
Protein kinase N2 regulates AMP kinase signaling and insulin responsiveness of glucose metabolism in skeletal muscle
Insulin resistance is central to the development of type 2 diabetes and related metabolic disorders. Because skeletal muscle is responsible for the majority of whole body insulin-stimulated glucose uptake, regulation of glucose metabolism in this tissue is of particular importance. Although Rho GTPases and many of their affecters influence skeletal muscle metabolism, there is a paucity of information on the protein kinase N (PKN) family of serine/threonine protein kinases. We investigated the impact of PKN2 on insulin signaling and glucose metabolism in primary human skeletal muscle cells in vitro and mouse tibialis anteri...
Source: AJP: Endocrinology and Metabolism - October 1, 2017 Category: Endocrinology Authors: Ruby, M. A., Riedl, I., Massart, J., Ahlin, M., Zierath, J. R. Tags: Research Article Source Type: research
High, but not low, exercise volume shifts the balance of renin-angiotensin system toward ACE2/Mas receptor axis in skeletal muscle in obese rats
This study aimed to evaluate volume exercise effects comparing low vs. high volume of chronic aerobic exercise on RAS axes in skeletal muscle in a diet-induced obesity (DIO) rat model. For this, male Wistar-Kyoto rats were fed a standard chow (SC) diet or a high-fat (HF) diet for 32 wk. Animals receiving the HF diet were randomly divided into low exercise volume (LEV, 150 min/wk) and high exercise volume (HEV, 300 min/wk) at the 20th week. After 12 wk of aerobic treadmill training, the body mass and composition, blood pressure, glucose and lipid metabolism, RAS axes, insulin signaling, and inflammatory pathway were perform...
Source: AJP: Endocrinology and Metabolism - October 1, 2017 Category: Endocrinology Authors: Frantz, E. D. C., Giori, I. G., Machado, M. V., Magliano, D. C., Freitas, F. M., Andrade, M. S. B., Vieira, A. B., Nobrega, A. C. L., Tibirica, E. Tags: Research Article Source Type: research
Changes in LXR signaling influence early-pregnancy lipogenesis and protect against dysregulated fetoplacental lipid homeostasis
Human pregnancy is associated with enhanced de novo lipogenesis in the early stages followed by hyperlipidemia during advanced gestation. Liver X receptors (LXRs) are oxysterol-activated nuclear receptors that stimulate de novo lipogenesis and also promote the efflux of cholesterol from extrahepatic tissues followed by its transport back to the liver for biliary excretion. Although LXR is recognized as a master regulator of triglyceride and cholesterol homeostasis, it is unknown whether it facilitates the gestational adaptations in lipid metabolism. To address this question, biochemical profiling, protein quantification, a...
Source: AJP: Endocrinology and Metabolism - October 1, 2017 Category: Endocrinology Authors: Nikolova, V., Papacleovoulou, G., Bellafante, E., Borges Manna, L., Jansen, E., Baron, S., Abu-Hayyeh, S., Parker, M., Williamson, C. Tags: Research Article Source Type: research
