• Animal cells and systems
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• v.13 no.4
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• pp.371-379
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• 2009

The endocannabinoid system (ECS) plays a key role in the regulation of appetite, body weight and metabolism. We undertook the present study to further clarify the regulation of the cannabinoid CB1 receptor (CB1, CNR1) in human adipose tissue in obesity. CB1 receptor mRNA expression was ~1.6-fold (p<0.004) and 1.9-fold higher (P<0.05) in subcutaneous adipocytes from obese compared to non-obese subjects in microarray and quantitative real-time PCR studies, respectively. Higher CB1 receptor mRNA expression levels in both adipose tissue (~1.2 fold, P<0.05) and adipocytes (~2 fold, P<0.01) were observed in samples from visceral compared to subcutaneous depots collected from 22 obese individuals. Immunofluorescence confocal microscopy demonstrated the presence of CB1 receptor on adipocytes and also adipose tissue macrophages. These data indicate that adipocyte CB1 receptor is up-regulated in human obesity and visceral adipose tissue and also suggest a potential role for the ECS in modulating immune/inflammation as well as fat metabolism in adipose tissue.

• Biomedical Science Letters
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• v.11 no.2
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• pp.89-101
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• 2005

Obesity is increasing worldwide and has become a major health burden in Western societies affecting every third American and every fifth European. Obesity makes a major contribution to morbidity and mortality, predisposing individuals to cardiovascular disease and diabetes. Many new substances are currently being investigated for their usefulness in the pharmacotherapy of obesity. Most anti-obesity drugs can be divided into four groups: those that reduce food intake; those that alter metabolism; those that increase thermogenesis; and those that regulate hormone involved in feeding behavior. In this article we review these and other agents available in various countries for the treatment of obesity. Perhaps more importantly, we have focussed on areas of potential productivity in the future. Over the last 5 or so years, this impetus in obesity research has provided us with exciting new drugs targets involved in the regulation of feeding behavior and cellular mechanism involved in energy expenditure. Recent development in the quest for control of human obesity include the discovery of hormones, neuropeptides, receptors and transcription factors involved in feeding behavior, metabolic rate and adipocyte development. For developing new, perhaps even more specific pharmacological agents, further research is needed to understand the individual different genetic and physiological basis of obesity. It remains the hope of research scientists that in the not too distant future we shall see a new class of anti-obesity drugs arising logically from the molecular biology revolutions.

• Molecules and Cells
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• v.45 no.4
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• pp.169-176
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• 2022

A primary cilium, a hair-like protrusion of the plasma membrane, is a pivotal organelle for sensing external environmental signals and transducing intracellular signaling. An interesting linkage between cilia and obesity has been revealed by studies of the human genetic ciliopathies Bardet-Biedl syndrome and Alström syndrome, in which obesity is a principal manifestation. Mouse models of cell type-specific cilia dysgenesis have subsequently demonstrated that ciliary defects restricted to specific hypothalamic neurons are sufficient to induce obesity and hyperphagia. A potential mechanism underlying hypothalamic neuron cilia-related obesity is impaired ciliary localization of G protein-coupled receptors involved in the regulation of appetite and energy metabolism. A well-studied example of this is melanocortin 4 receptor (MC4R), mutations in which are the most common cause of human monogenic obesity. In the paraventricular hypothalamus neurons, a blockade of ciliary trafficking of MC4R as well as its downstream ciliary signaling leads to hyperphagia and weight gain. Another potential mechanism is reduced leptin signaling in hypothalamic neurons with defective cilia. Leptin receptors traffic to the periciliary area upon leptin stimulation. Moreover, defects in cilia formation hamper leptin signaling and actions in both developing and differentiated hypothalamic neurons. The list of obesity-linked ciliary proteins is expending and this supports a tight association between cilia and obesity. This article provides a brief review on the mechanism of how ciliary defects in hypothalamic neurons facilitate obesity.

• BMB Reports
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• v.56 no.10
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• pp.527-536
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• 2023

Serotonin receptors, also known as 5-HT receptors, belong to the G protein-coupled receptors (GPCRs) superfamily. They mediate the effects of serotonin, a neurotransmitter that plays a key role in a wide range of functions including mood regulation, cognition and appetite. The functions of serotonin are mediated by a family of 5-HT receptors including 12 GPCRs belonging to six major families: 5-HT₁, 5-HT₂, 5-HT₄, 5-HT₅, 5-HT₆ and 5-HT₇. Despite their distinct characteristics and functions, these receptors' subtypes share common structural features and signaling mechanisms. Understanding the structure, functions and pharmacology of the serotonin receptor family is essential for unraveling the complexities of serotonin signaling and developing targeted therapeutics for neuropsychiatric disorders. However, developing drugs that selectively target specific receptor subtypes is challenging due to the structural similarities in their orthosteric binding sites. This review focuses on the recent advancements in the structural studies of 5-HT receptors, highlighting the key structural features of each subtype and shedding light on their potential as targets for mental health and neurological disorders (such as depression, anxiety, schizophrenia, and migraine) drugs.

• Archives of Obesity and Metabolism
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• v.2 no.2
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• pp.45-53
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• 2023

Despite the emergence of obesity as a significant public health concern, artificial sweeteners have made their way into various food products due to the perception, that they serve as substitutes for sugar. Artificial sweeteners are used to supposedly achieve weight management and health improvement. However, their efficacy and safety remain debatable. Commonly used artificial sweeteners include aspartame, acesulfame potassium, saccharin, and sucralose. This article discusses the effects of artificial sweetener consumption on weight loss, appetite regulation, blood glucose control, and gut microbiota. Research findings, concerning the consumption of artificial sweeteners and their association with body weight, have shown inconsistencies between randomized controlled trials and cohort studies. Studies, comparing artificial sweeteners to sugar, have reported no significant differences in satiety. Although artificial sweeteners have no calories, they can affect blood sugar levels through the cephalic phase insulin response. A recent study suggested that artificial sweeteners influenced the occurrence of diabetes. Due to limitations in the study design, excluding diabetes-influencing factors was not feasible. The evidence showed that artificial sweeteners harbored potential health risks, necessitating further investigation. According to recent studies, the consumption of artificial sweeteners was associated with gut microbiota changes and individual blood sugar responses. It is important to note that artificial sweeteners cannot be considered safe alternatives to sugar, and further research is required.

• Journal of the Korean Society of Food Science and Nutrition
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• v.37 no.4
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• pp.428-436
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• 2008

This study was carried out to compare the effects of whey protein concentrate, its hydrolysates and macropeptide fractions obtained from papain treatment of whey protein on lipid levels and appetite-related hormones in obesity model rats induced by high fat diet. Four week-old male Sprague-Dawley rats were fed high fat (18% w/w) and low protein (10% w/w) diet for 4 weeks and then divided into four groups (n=8/group). Rats were fed high fat diets containing various nitrogen sources; 10% whey protein concentrate (10WPC), 25% whey protein concentrate (25WPC), 25% whey protein hydrolysates (25WH), and 25% whey macropeptide fractions (25WP, MW$\geq$10,000), respectively for 6 weeks. There were no significant differences in body weight gain and food intake among groups. A significant decrease of total lipid, triglyceride in serum was observed in 25WH and 25WP groups. Total lipid and triglyceride contents of the liver were significantly decreased in 25WPC, 25WH and 25WP groups compared with 10WPC group. However, in the liver, there were no differences in the contents of total lipid and triglyceride among 25WPC, 25WH and 25WP groups. The daily amounts of feces were significantly increased in 25WH and 25WP groups and the excretion of total lipid and triglyceride were significantly increased in 25WH group. Serum glucose and insulin concentration were significantly decreased in 25WH group. The concentration of serum ghrelin was significantly decreased in the 25WPC, 25WH and 25WP groups compared with 10WPC group. However, there was no significant difference in the concentration of serum leptin among groups. These results suggest that whey protein hydrolysates and macropeptide fractions may show beneficial effects on the lipid profile in serum and liver, appetite regulation and insulin resistance in obesity model rats induced by high fat diet.

• Polymer(Korea)
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• v.30 no.4
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• pp.357-361
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• 2006

Alpha-lipoic acid (ALA) synthesized in the body has virtues such as anti-oxidation, blood sugar regulation, appetite suppression, and anti-obesity, etc. ALA, which is also used as a drug, has a five-membered ring including disulfide and so easily losses bioavailability due to ring opening and subsequent polymerization by heat or ultraviolet. This report studies various conditions for ring opening polymerization. The ring opening starts above the melting point of ALA, but there was no temperature dependence above it. At $70^{\circ}C$, the degree of ring opening was proportional to reaction time and inversely proportional concentration. The degree of ring opening in acetic acid with UV for 1 hour reached the maximum conversion (70%). Most cleaved ALA changed into disulfide polymers, and the molecular weight of the polymers increased as the amount of ring opening increased.

• Asian-Australasian Journal of Animal Sciences
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• v.21 no.10
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• pp.1473-1478
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• 2008

An experiment was conducted to investigate the mechanism for the effect of tetrabasic zinc chloride (TBZC) in enhancing growth performance of weanling piglets. Gut-brain peptides play an important role in the regulation of growth and appetite in animals. This study evaluated the effects of TBZC on blood concentrations of growth hormone (GH), ghrelin, insulin-like growth factor-I (IGF-I), cholecystokinin (CCK) and neuropeptide Y (NPY). Seventy-two weanling piglets (Landrace$\times$Large White) with an initial body weight (BW) of $6.7{\pm}0.16kg$ and aged $24{\pm}1days$ were assigned to three dietary treatments: i) control diet without TBZC supplement, ii) the control diet supplemented with 2,000 mg Zn from TBZC/kg and iii) TBZC-supplemented diet pair-fed with respect to the control diet. Each treatment had six replications (pens) of four piglets. At the end of a 14-d experimental period, piglets were weighed and feed consumption was measured, and blood samples were collected for assays of GH, ghrelin, IGF-I, CCK and NPY concentrations. The inclusion of TBZC in the diet increased average daily gain (p<0.01), average daily feed intake (p<0.05), and feed conversion ratio (p<0.05). Pair-fed piglets had higher ADG, and lower FCR than (p<0.05) Control piglets. Supplementation of the diet with TBZC increased (p<0.05) serum GH and plasma ghrelin levels in weanling piglets, but did not affect (p>0.05) serum IGF-I and plasma NPY and CCK concentrations. Pair-fed piglets had lower (p<0.05) serum GH levels than TBZC-supplemented piglets, but did not (p>0.05) differ from Control piglets. These data indicated that TBZC elevated the concentration of ghrelin and GH. This observation may partly explain the beneficial effects of TBZC on growth performance of weanling piglets.

• Journal of Korean Medicine for Obesity Research
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• v.15 no.2
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• pp.104-110
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• 2015

Objectives: The herb of Agastache rugosa (AR) is a traditional herbal medicine used for colds, vomiting and furuncles. However, there are few reports to investigate the inhibitory effects of AR on obesity. In this study, the effects of AR on high fat diet (HFD)-induced obesity and its mechanism of actions were investigated in experimental animals. Methods: The mice were fed HFD for 4 weeks to induce obesity. After randomly divided into normal fat diet, HFD and AR groups, 200 mg/kg of AR was administrated for 4 weeks with continuous HFD feeding while vehicle was orally treated to HFD group. Food intake and body weight were recorded weekly. Results: Increased body weight by HFD was improved by AR treatment. AR administration inhibited an increase of visceral fat weight as well as adipocyte hypertrophy. Hepatic steatosis was ameliorated in AR-treated mice. In addition, treatment of AR attenuated the expression of adipogenic transcription factor, peroxisome proliferator-activated receptor (PPAR)-gamma in the epididymal adipose tissue. Also the increased serum leptin level by HFD was maintained in AR group, leading to inhibition of food intake. Conclusions: AR treatment showed inhibitory effects on HFD-induced obesity by inhibition of PPAR-gamma and reduction of food intake. AR could be an alternative treatment for obesity.

• Genomics & Informatics
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• v.6 no.3
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• pp.117-125
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• 2008

Recently, obesity has become a worldwide public health concern and the use of anorectic drugs has drastically increased. In this study, sibutramine and phendimetrazine, representative marketed anorectics, were repeatedly administered per os on a daily basis into C57BL/6 mice and the effects of these drugs on food intakes, body weight changes and gene expression profiles were monitored for up to following 7 days. Methamphetamine, which has a potent anorectic effect, was used as a positive control. Anorectic effects were sustained only for two days by phendimetrazine or methamphetamine, but for six days by sibutramine. The modulations of gene expressions in the hypothalamus and the striatum were investigated using microarrays on day 2 and day 7 post-administration, which corresponded to the anorectic period and a return of appetite respectively, for all three drugs tested. Differences in overall gene expression profiles in the stratum on day 2 for sibutramine and phendimetrazine seems to reflect difference between the two in terms of the onsets of drug tolerance. According to microarray findings, the Ankrd26 gene appears to have an important anorectic role, whereas the up-regulation of the olfaction system appeared to be involved in the drug tolerance of anorectics. The microarray data presented in this study demonstrates the usefulness of gene expression analysis for gathering information on the efficacy and safety of anorectic drugs.