scholarly journals Could there be a fine-tuning role for brain-derived adipokines in the regulation of bodyweight and prevention of obesity?

2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Russell E. Brown

Obesity is one of the most prevalent medical conditions, often associated with several negative stereotypes. Although it is true that weight gain occurs when food intake exceeds energy expenditure, it is important to note that even a 1% mismatch between the two can lead to a substantial weight gain after only a few years. Further, the body appears to balance energy metabolism via an endogenous lipostatic loop in which adipose stores send hormonal signals (e.g. adipokines such as leptin) to the hypothalamus in order to reduce appetite and increase energy expenditure. However, the brain is also a novel site of expression of many of these adipokine genes. This led to the hypothesis that hypothalamic-derived adipokines might also be involved in bodyweight regulation by exerting some effect on the control of appetite or hypothalamic function. When RNA interference (RNAi) was used to specifically silence adipokine gene expression in various in vitro models, this led to increases in cell death, modification of the expression of key signaling genes (i.e. suppressor of cytokine signaling-3; SOCS-3), and modulation of the activation of cellular energy sensors (i.e. adenosine monophosphate-activated protein kinase; AMPK). Subsequently, when RNAi was used to inhibit the expression of brain-derived leptin in adult rats this resulted in minor increases in weight gain in addition to modifying the expression of other adipokine genes (eg. resistin). In summary, although adipokines secreted by adipose tissue appear to the main regulator of lipostatic loop, this review shows that the fine tuning that is required to maintain a stable bodyweight by this system might be accomplished by hypothalamic-derived adipokines. Perturbations in this central adipokine system could lead to alterations in normal hypothalamic function which leads to unintended weight gain.

Author(s):  
Woo Nam ◽  
Seok Hyun Nam ◽  
Sung Phil Kim ◽  
Carol Levin ◽  
Mendel Friedman

Abstract Background The body responds to overnutrition by converting stem cells to adipocytes. In vitro and in vivo studies have shown polyphenols and other natural compounds to be anti-adipogenic, presumably due in part to their antioxidant properties. Purpurin is a highly antioxidative anthraquinone and previous studies on anthraquinones have reported numerous biological activities in cells and animals. Anthraquinones have also been used to stimulate osteoblast differentiation, an inversely-related process to that of adipocyte differentiation. We propose that due to its high antioxidative properties, purpurin administration might attenuate adipogenesis in cells and in mice. Methods Our study will test the effect purpurin has on adipogenesis using both in vitro and in vivo models. The in vitro model consists of tracking with various biomarkers, the differentiation of pre-adipocyte to adipocytes in cell culture. The compound will then be tested in mice fed a high-fat diet. Murine 3T3-L1 preadipocyte cells were stimulated to differentiate in the presence or absence of purpurin. The following cellular parameters were measured: intracellular reactive oxygen species (ROS), membrane potential of the mitochondria, ATP production, activation of AMPK (adenosine 5′-monophosphate-activated protein kinase), insulin-induced lipid accumulation, triglyceride accumulation, and expression of PPARγ (peroxisome proliferator activated receptor-γ) and C/EBPα (CCAAT enhancer binding protein α). In vivo, mice were fed high fat diets supplemented with various levels of purpurin. Data collected from the animals included anthropometric data, glucose tolerance test results, and postmortem plasma glucose, lipid levels, and organ examinations. Results The administration of purpurin at 50 and 100 μM in 3T3-L1 cells, and at 40 and 80 mg/kg in mice proved to be a sensitive range: the lower concentrations affected several measured parameters, whereas at the higher doses purpurin consistently mitigated biomarkers associated with adipogenesis, and weight gain in mice. Purpurin appears to be an effective antiadipogenic compound. Conclusion The anthraquinone purpurin has potent in vitro anti-adipogenic effects in cells and in vivo anti-obesity effects in mice consuming a high-fat diet. Differentiation of 3T3-L1 cells was dose-dependently inhibited by purpurin, apparently by AMPK activation. Mice on a high-fat diet experienced a dose-dependent reduction in induced weight gain of up to 55%.


2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 503-503
Author(s):  
Zhiji Huang ◽  
Yafang Ma ◽  
Chunbao Li

Abstract Objectives Kappa-Carrageenan(CGN) is a widely used food additive in the meat industry and a highly viscous soluble dietary fiber which can hardly be fermented. It has been shown to be able to regulate the energy metabolism and inhibit diet-induced obesity. However, the mechanism is not well understood. The purpose of this study is to investigate the mechanisms of κ-carrageenan to inhibit the body weight gain. Methods A high-fat diet incorporated with lard, pork protein and CGN (2% or 4%, w/w) was given to C57BL/6J mice for 90 days. The energy intake and weight changes were measured every three days. After the dietary intervention, mice were sacrificed, liver and epididymal adipose tissues were taken for real-time polymerase chain reaction (RT-qPCR) analysis. Results The CGN in the high-fat diet restricted weight gain by decreasing liver and adipose mass without inhibiting energy intake.  The genes involving energy expenditure such as Acox1, Acadl, CPT-1A and Sirt1 were upregulated in the mice fed with carrageenan. However, the genes responsible for lipid synthesis were not significantly different compared to the diet-induced obese model. Conclusions The anti-obesity effect of the CGN in high-fat diet could be highly related to the enhancement of energy expenditure through up-regulating the downstream genes which promote β-oxidation by increasing the Sirt1 gene expression in liver. Funding Sources Ministry of Science and Technology of the People's Republic of China (10000 Talent Project)


2008 ◽  
Vol 82 (19) ◽  
pp. 9537-9545 ◽  
Author(s):  
Marion Poenisch ◽  
Sandra Wille ◽  
Peter Staeheli ◽  
Urs Schneider

ABSTRACT An unusually long noncoding sequence is located between the N gene of Borna disease virus (BDV) and the genes for regulatory factor X and polymerase cofactor P. Most of these nucleotides are transcribed and seem to control translation of the bicistronic X/P mRNA. We report here that Vero cells persistently infected with mutant viruses containing minor alterations in this control region showed almost normal levels of N, X, and P proteins but exhibited greatly reduced levels of mRNAs coding for these viral gene products. Surprisingly, cells infected with these BDV mutants accumulated a viral transcript 1.9 kb in length that represents a capped and polyadenylated mRNA containing the coding regions of the N, X, and P genes. Cells infected with wild-type BDV also contained substantial amounts of this read-through mRNA, which yielded both N and P protein when translated in vitro. Viruses carrying mutations that promoted read-through transcription at the first gene junction failed to replicate in the brain of adult rats. In the brains of newborn rats, these mutant viruses were able to replicate after acquiring second-site mutations in or near the termination signal located downstream of the N gene. Thus, sequence elements adjacent to the core termination signal seem to regulate the frequency by which the polymerase terminates transcription after the N gene. We conclude from these observations that BDV uses read-through transcription for fine-tuning the expression of the N, X, and P genes which, in turn, influence viral polymerase activity.


2018 ◽  
Vol 315 (3) ◽  
pp. F413-F416 ◽  
Author(s):  
Aaron L. Brown ◽  
Maurice B. Fluitt ◽  
Carolyn M. Ecelbarger

The renal collecting duct and other postmacula densa sites are the primary tubular regions for fine-tuning of electrolyte homeostasis in the body. A role for the mechanistic target of rapamycin (mTOR), a serine-threonine kinase, has recently been appreciated in this regulation. mTOR exists in two distinct multiprotein functional complexes, i.e., mTORC1 and mTORC2. Upregulation of mTORC1, by growth factors and amino acids, is associated with cell cycle regulation and hypertrophic changes. In contrast, mTORC2 has been demonstrated to have a role in regulating Na+ and K+ reabsorptive processes, including those downstream of insulin and serum- and glucocorticoid-regulated kinase (SGK). In addition, mTORC2 can upregulate mTORC1. A number of elegant in vitro and in vivo studies using cell systems and genetically modified mice have revealed mechanisms underlying activation of the epithelial Na+ channel (ENaC) and the renal outer medullary K+ channel (ROMK) by mTORC2. Overall, mTOR in its systematic integration of phosphorylative signaling facilitates the delicate balance of whole body electrolyte homeostasis in the face of changes in metabolic status. Thus, inappropriate regulation of renal mTOR has the potential to result in electrolyte disturbances, such as acidosis/alkalosis, hyponatremia, and hypertension. The goal of this minireview is to highlight the physiological role of mTOR in its complexes in regulating electrolyte homeostasis in the aldosterone-sensitive distal nephron.


Author(s):  
H. Kettunen ◽  
E. van Eerden ◽  
K. Lipiński ◽  
T. Rinttilä ◽  
E. Valkonen ◽  
...  

SummaryResin acid composition (RAC) has previously been shown to inhibit the growth of the Gram-positive bacterial species Clostridium perfringens in vitro and to modulate the ileal microbiota of broiler chickens. The following trials examined the effect of RAC on broiler chickens in two experiments. In experiment 1, 1400 one-day-old Ross 308 broilers were divided into two coccidiostat treatments: chemical (CC) and ionophore (IC), which were further divided into two RAC dosages: 0 and 0.5 g/kg. All diets were supplemented with xylanase, β-glucanase and phytase feed enzymes. The birds were raised in a commercial-type environment without additional microbial challenge during the 42-day trial. RAC improved the body weight gain by 3.3% and feed conversion ratio by 5.7% with CC, and improved footpad lesion scores with IC but had no effect on the litter quality. Experiment 2 was a 35-day subclinical necrotic enteritis (NE) challenge trial with 510 male Ross 308 chickens. The dietary treatments included a non-challenged, non-supplemented control and four NE challenged treatments with dietary RAC supplementation at 0, 1, 2, and 3 g/kg. The birds were challenged with Eimeria maxima on day nine and C. perfringens on day 14. While RAC at 1 g/kg significantly increased bird weight gain during the challenge, it did not affect the microbial or short chain fatty acid (SCFA) profiles. In contrast, RAC at 3 g/kg reduced the abundance of the Lactobacillus group and tended to reduce the abundance of genus Bifidobacterium and the total numbers of eubacteria. These experiments suggest that dietary RAC at a moderate dose positively affected broiler performance. However, changes in caecal microbiota populations may not have influenced the observed performance effects of RAC.


2006 ◽  
Vol 1 (2) ◽  
pp. 221-234 ◽  
Author(s):  
Kajsa Sjöholm ◽  
Björn Carlsson ◽  
Lena Carlsson

AbstractThe leptin system regulates body fat mass through a feedback loop between adipose tissue and the hypothalamus. To test if leptin responsiveness may be regulated we assayed hypothalamic response to leptin during the estrous cycle; when changes in food intake are known to occur. Immature rats were treated with pregnant mare’s serum gonadotropin (PMSG) to induce synchronized follicular development, ovulation and corpus luteum formation. Leptin response was estimated by measuring the in vitro induction of tis11, a primary response gene activated by STAT3-dependent cytokines in hypothalamic explants after leptin stimulation. In addition, mRNA levels of the suppressor cytokine signaling-3 (SOCS-3), a possible mediator of leptin resistance, were analyzed. Serum leptin levels did not change between days 2 and day 3 (corresponding to proestrus and estrus, respectively) but the response to leptin was higher on day 2 than on day 3 (p=0.05). Food intake displayed a tendency towards downregulation between day 1 and day 2 (p=0.057), and a tendency towards upregulation between day 2 and day 3 (p=0.072), although the body weight increased on day of the study (p<0.0001). There was no significant difference in hypothalamic expression of SOCS-3 between day 2 and day 3. In conclusion, we have shown that leptin responsiveness changes during a hormonally induced estrous cycle in rats. Our data suggest that a change in the hypothalamic response to leptin may cause the cyclic feeding behavior seen in rats.


2016 ◽  
Vol 7 (1) ◽  
pp. 35-44 ◽  
Author(s):  
S. Asghar ◽  
M. Arif ◽  
M. Nawaz ◽  
K. Muhammad ◽  
M.A. Ali ◽  
...  

Aim of the present study was to characterise and evaluate probiotic potential of lactobacilli isolated from indigenous poultry. Lactobacilli were isolated from poultry droppings and identified by genus specific polymerase chain reaction and 16S rRNA gene sequencing. Isolates were characterised in vitro by their ability to tolerate low pH and bile salts, phytase activity, antimicrobial activity, antibiotic susceptibility profile, and autoaggregation and coaggregation with poultry gut pathogens. In vivo evaluation of selected isolates was done by their effect on the body weight gain and immune response of broiler chicks. Total of 90, one-day old chicks, were randomly divided in 9 groups and given selected lactobacilli alone and in combinations (108 cfu/bird, daily) from day 7 to day 35. Body weight gain and humoral immune response to New Castle Disease Virus (NDV) vaccine were determined weekly. Three lactobacilli isolates (SMP52, SMP64 and SMP70) were selected as potentially probiotic bacteria on the basis of in vitro characterisation and identified as Lactobacillus crispatus, Lactobacillus casei and L. crispatus, respectively. Chicks supplemented with ‘SMP52’, ‘SMP64’, ‘SMP70’ and ‘SMP64+SMP70’ and a commercial probiotic product (Protexin) showed significantly higher mean weight gain per bird (1,584±35.2, 1,629±30.6, 1,668±34.7, 1,619±29.5 and 1,576±31.7 g/bird, respectively) as compared to negative control group (1,394±26.7 g/bird), on day 35. SMP 70 also showed significantly higher geometric mean titre against NDV vaccine at day 21 as compared to negative control. It is concluded that L. crispatus SMP52, L. casei SMP64 and L. crispatus SMP70 are potential probiotic candidates which alone or in different combinations may increase body weight of broilers.


2007 ◽  
Vol 293 (5) ◽  
pp. R1855-R1863 ◽  
Author(s):  
Christine Mack ◽  
Julie Wilson ◽  
Jennifer Athanacio ◽  
James Reynolds ◽  
Kevin Laugero ◽  
...  

The ability of amylin to reduce acute food intake in rodents is well established. Longer-term administration in rats (up to 24 days) shows a concomitant reduction in body weight, suggesting energy intake plays a significant role in mediating amylin-induced weight loss. The current set of experiments further explores the long-term effects of amylin (4–11 wk) on food preference, energy expenditure, and body weight and composition. Furthermore, we describe the acute effect of amylin on locomotor activity and kaolin consumption to test for possible nonhomeostatic mechanisms that could affect food intake. Four-week subcutaneous amylin infusion of high-fat fed rats (3–300 μg·kg−1·day−1) dose dependently reduced food intake and body weight gain (ED50for body weight gain = 16.5 μg·kg−1·day−1). The effect of amylin on body weight gain was durable for up to 11 wks and was associated with a specific loss of fat mass and increased metabolic rate. The body weight of rats withdrawn from amylin (100 μg·kg−1·day−1) after 4 wks of infusion returned to control levels 2 wks after treatment cessation, but did not rebound above control levels. When self-selecting calories from a low- or high-fat diet during 11 wks of infusion, amylin-treated rats (300 μg·kg−1·day−1) consistently chose a larger percentage of calories from the low-fat diet vs. controls. Amylin acutely had no effect on locomotor activity or kaolin consumption at doses that decreased food intake. These results demonstrate pharmacological actions of amylin in long-term body weight regulation in part through appetitive-related mechanisms and possibly via changes in food preference and energy expenditure.


Author(s):  
Yunxia Zhang ◽  
Jin Li ◽  
Hui-hui Wang ◽  
Jiao Li ◽  
Yue Yu ◽  
...  

Despite all modern advances in medicine, there are few reports of effective and safe drugs to treat obesity. Our objective was to screen anti-obesity natural compounds, and to verify whether they can reduce the body weight gain and investigate their molecular mechanisms. By using drug-screening methods, Phytohemagglutinin (PHA) was found to be the most anti-obesity candidate natural compound. Six-week-old C57BL/6J mice were fed with high-fat diet (HFD) and intraperitoneally injected with 0.25mg/kg PHA every day for 8 weeks. The body weight, glucose homeostasis, oxygen consumption and physical activity were assessed. We also measured the heat intensity, body temperature and the gene expression of key regulators of energy expenditure. Prevention study results showed PHA treatment not only reduced the body weight gain, but also maintained glucose homeostasis in HFD-fed mice. Further study indicated energy expenditure and uncoupling protein 1 (UCP-1) expression of brown adipose tissue (BAT) and white adipose tissue (WAT) in HFD-fed mice were significantly improved by PHA. In the therapeutic study, the similar effect was observed. PHA inhibited lipid droplet formation and up-regulated mitochondrial related genes expression during adipogenesis in vitro. UCP-1 KO mice displayed no differences in body weight, glucose homeostasis and core body temperature between PHA and control groups. Our results suggest that PHA prevent and treat obesity by increasing energy expenditure though up-regulation of BAT thermogenesis.


2011 ◽  
Vol 40 (6) ◽  
pp. 1296-1302
Author(s):  
Felipe Jochims ◽  
Cleber Cassol Pires ◽  
Alexandre Lins ◽  
Luana Cortez Zago ◽  
Guilherme Mello Jahn ◽  
...  

The objective of this study was to evaluate the performance of Texel × Ile de France female hoggets on pearl millet (Pennisetum americanum (L.) Leeke) pastures fed supplementation with cassava meal or corn gluten. It was used a completely randomized experimental design, with three treatments (feed strategies) and two area replications. Feed strategies consisted of supplementation of the pastures with cassava meal or corn gluten in comparison to exclusive pasture. Supplements were given daily at 9:00 a.m. at quantity of 1% of the body weight (BW). The lambs on corn gluten supplementation presented greater daily weight gain and greater per area weight gain. Use of supplementation did not permit to increase pasture stocking rate, however. In vitro digestibility and chemical composition of the harvested forage was similar (crude protein, neutral detergent fiber) among groups. At the end of the experiment, all feed strategies were efficient in promoting weight greater than 60% of the mature weight, showing that the lambs are able for mating. Body condition score (BCS) of lambs under cassava meal supplementation was 3.0 whereas body composition score of the other lambs was 2.8. Exclusive use of pearl millet can provide dry matter requirement of the lambs.


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