Jiao Guo

Advances in understanding the interrelations between leptin resistance and obesity

Obesity, which has developed into a global epidemic, is a risk factor in most chronic diseases and some forms of malignancy. The discovery of leptin in 1994 has opened a new field in obesity research. Currently, we know that leptin is the primary signal from energy stores and exerts negative feedback effects on energy intake. However, most individuals with diet-induced obesity (DIO) develop leptin resistance, which is characterized by elevated circulating leptin levels and decreased leptin sensitivity. To date, though various mechanisms have been proposed to explain leptin resistance, the exact mechanisms of leptin resistance in obesity are poorly understood. Consequently, its an important issue worth discussing regarding what the exact interrelations between leptin resistance and obesity are. Here, we review the latest advancements in the molecular mechanisms of leptin resistance and the exact interrelations between leptin resistance, obesity, and obesity-related diseases, in order to supply new ideas for the study of obesity.

Anti-Obese Effect of Glucosamine and Chitosan Oligosaccharide in High-Fat Diet-Induced Obese Rats

Objective: This study is to evaluate the anti-obese effects of glucosamine (GLC) and chitosan oligosaccharide (COS) on high-fat diet-induced obese rats. Methods: The rats were randomly divided into twelve groups: a normal diet group (NF), a high-fat diet group (HF), Orlistat group, GLC high-, middle-, and low-dose groups (GLC-H, GLC-M, GLC-L), COS1 (COS, number-average molecular weight ≤1000) high-, middle-, and low-dose groups (COS1-H, COS1-M, COS1-L), and COS2 (COS, number-average molecular weight ≤3000) high-, middle-, and low-dose groups (COS2-H, COS2-M, COS2-L). All groups received oral treatment by gavage once daily for a period of six weeks. Results: Rats fed with COS1 gained the least weight among all the groups (P < 0.01), and these rats lost more weight than those treated with Orlistat. In addition to the COS2-H and Orlistat groups, the serum total cholesterol (CHO) and low-density lipoprotein cholesterol (LDL-C) levels were significantly reduced in all treatment groups compared to the HF group (P < 0.01). The various doses of GLC, COS1 and COS2 reduced the expression levels of PPARγ and LXRα mRNA in the white adipose tissue. Conclusions: The results above demonstrated that GLC, COS1, and COS2 improved dyslipidemia and prevented body weight gains by inhibiting the adipocyte differentiation in obese rats induced by a high-fat diet. Thus, these agents may potentially be used to treat obesity.

Hypolipidemic effects of chitosan and its derivatives in hyperlipidemic rats induced by a high-fat diet

Background Hyperlipidemia (HLP) is the primary risk factor of cardiovascular disease (CVD). Various factors, including genetics, physical inactivity, and daily nutritional habits, affect the prevalence of HLP. Recently, it was revealed that dietary fibers, such as pectin, psyllium, and especially chitosan (CTS), may play important roles in hypolipidemic management. Thus, this study aims to determine the hypolipidemic effect and mechanism of CTS and its water-soluble derivatives, chitosan oligosaccharides (MN≤1,000 Da (COSI) and MN≤3,000 Da (COSIII)), in male hyperlipidemic rats induced by a high-fat diet (HFD). Design After the model creation, 120 Sprague-Dawley (SD) rats were equally assigned to 12 groups fed various diets as follows: the normal group with basic diet, an HFD group, an HFD group supplemented with three doses of CTS, COSI and COSIII groups, and an HFD group treated with simvastatin (7 mg/kg·d). After 6 weeks, body weight, fat/body ratio, and the relevant biomarkers of serum, liver, and feces were measured. Additionally, the histological analysis of liver and adipose tissue was performed, and the mRNA expressions of liver peroxisome proliferator-activated receptor-α (PPARα) and hepatic lipase (HL) were examined. Results Compared with HFD group, rats fed CTS, COSI, and COSIII showed a better ability to regulate their body weight, liver and cardiac indices, fat/body ratio, as well as serum, liver, and fecal lipids, and simultaneously to maintain the appropriate activity of liver and serum superoxide dismutase (SOD), alanine aminotransferase (ALT), aspartate aminotransferase (AST), as well as liver and fecal total bile acids (TBA). Simultaneously, there had been a higher mRNA expression of PPARα and HL in the treatment groups. Conclusion The obtained results suggested that these three function foods can effectively improve liver lipid metabolism by normalizing the expressions of PPARα and HL, and protect liver from the oxidized trauma by enhancing hepatic function, which could be potentially used to remedy hyperlipidemia.

The Preparation of Capsaicin-Chitosan Microspheres (CCMS) Enteric Coated Tablets

This study aimed to research the preparation and content determination of capsaicin-chitosan microspheres (CCMS) enteric coated tablets. The core tablets were prepared with the method of wet granulation. Nine formulae were designed to determine the optimal formula of the core tablet. Eudragit L100 was used to prepare the CCMS enteric-coated tablets. The effect of enteric coated formulation variables such as content of talc (10%, 25% and 40%), plasticisers (TEC and DBS), dosage of plasticiser (10%, 20% and 30%) and coating weight (2%, 3% and 5%) were evaluated for drug release characteristics. The in vitro release was studied using 0.1 N HCl and pH 6.8 phosphate buffer. Enteric coated tablets without ruptures or swelling behaviour over 2 h in 0.1 N HCl indicated that these tablets showed acid resistance. The accumulated release rate in phosphate buffer (pH 6.8) revealed that the prepared tablets were able to sustain drug release into the intestine and a first-order release was obtained for capsaicin. This research is the first report of the preparation and content determination of CCMS enteric coated tablets. The sustained release behavior of enteric coated formulations in pH 6.8 phosphate buffer demonstrated that it would be a potential drug delivery platform for sustained delivery of gastric irritant drugs.

The effect of chitooligosaccharides on oleic acid-induced lipid accumulation in HepG2 cells

This experiment aimed to evaluate the capacities of two types of chitooligosaccharides (COS) with different molecular weights for the ability to eliminate lipid accumulation in hepatocytes. We have established a lipid accumulation model in HepG2 cells for these studies in vitro, which was established by induction with oleic acid. The capacity of COS to eliminate lipid accumulation was evaluated using three metrics: the thiazolyl blue dye absorbance (MTT value), the morphology of intracellular lipid droplets and the triglyceride level (TG). Two types of COS with different molecular weights (1000 Da and 3000 Da) can significantly reduce intracellular lipid accumulation and decrease TG content in HepG2 cells, in a dose-dependent fashion. We found that low molecular weight COS is more efficacious than high molecular weight COS. Two types of COS can eliminate lipid accumulation induced by oleic acid in HepG2 cells, leading to an obvious hypolipidemic effect in vitro. These results suggest that COS may be effective preventive agents in fatty liver disease.

The Status of Research into Resistance to Diet-Induced Obesity

Obesity resistance is an increasingly popular area of study in academia, although the factors that lead to the occurrence of obesity resistance remain unclear. In this review, we discuss the currently known causes of obesity resistance. By comparing the differences between obesity-resistant individuals and obesity-susceptible individuals, researchers have identified the characteristics of obesity-resistant individuals. The primary approach has been to breed rats and mice with a high-fat diet and to compare the differences between obesity-resistant and obesity-susceptible individuals. The characterized differences have included gastrointestinal fat absorption, appetite, physical activity, fat storage, and fat consumption. Considerably more research is needed into the mechanisms of obesity resistance that could be used to lose weight among human subjects. However, there are few ongoing obesity resistance studies. Due to the relatively slow rate of development in this field, greater efforts must be applied in this area.

Hypothalamic endoplasmic reticulum stress as a key mediator of obesity-induced leptin resistance: Obesity, leptin resistance and ER stress

Obesity is an epidemic disease that is increasing worldwide and is a major risk factor for many metabolic diseases. However, effective agents for the prevention or treatment of obesity remain limited. Therefore, it is urgent to clarify the pathophysiological mechanisms underlying the development and progression of obesity and exploit potential agents to cure and prevent this disease. According to a recent study series, obesity is associated with the development of endoplasmic reticulum stress and the activation of its stress responses (unfolded protein response) in metabolically active tissues, which contribute to the development of obesity‐related insulin and leptin resistance, inflammation and energy imbalance. Hypothalamic endoplasmic reticulum stress is the central mechanism underlying the development of obesity‐associated leptin resistance and disruption of energy homeostasis; thus, targeting endoplasmic reticulum stress offers a promising therapeutic strategy for improving leptin sensitivity, increasing energy expenditure and ultimately combating obesity. In this review, we highlight the relationship between and mechanism underlying hypothalamic endoplasmic reticulum stress and obesity‐associated leptin resistance and energy imbalance and provide new insight regarding strategies for the treatment of obesity.

Complex Relationship between Obesity and the Fat Mass and Obesity Locus

In the 21st century, obesity has become a serious problem because of increasing obese patients and numerous metabolic complications. The primary reasons for this situation are environmental and genetic factors. In 2007, FTO (fat mass and obesity associated) was the first gene identified through a genome-wide association study (GWAS) associated with obesity in humans. Subsequently, a cluster of single nucleotide polymorphisms (SNPs) in the first intron of the FTO gene was discovered to be associated with BMI and body composition. Various studies have explored the mechanistic basis behind this association. Thus, emerging evidence showed that FTO plays a key role regulating adipose tissue development and functions in body size and composition. Recent prevalent research topic concentrated in the three neighboring genes of FTO: RPGRIP1L, IRX3 and IRX5, as having a functional link between obesity-associated common variants within FTO and the observed human phenotypes. The purpose of this review is to present a comprehensive picture of the impact of FTO on obesity susceptibility and to illuminate these new studies of FTO function in adipose tissue.

Determination of the Deacetylation Degree of Chitooligosaccharides

The methods for determination of chitosan content recommended in the Chinese Pharmacopoeia and the European Pharmacopoeia are not applicable for evaluation of the extent of deacetylation (deacetylation degree, DD) in chitooligosaccharides (COS). This study explores two different methods for assessment of DD in COS having relatively high and low molecular weights: an acid-base titration with bromocresol green indicator and a first order derivative UV spectrophotometric method for assessment of DD in COS. The accuracy of both methods as a function of molecular weight was also investigated and compared to results obtained using 1H NMR spectroscopy. Our study demonstrates two simple, fast, widely adaptable, highly precise, accurate, and inexpensive methods for the effective determination of DD in COS, which have the potential for widespread commercial applications in developing country.

In vitro inhibition of lipid accumulation induced by oleic acid and in vivo pharmacokinetics of chitosan microspheres (CTMS) and chitosan-capsaicin microspheres (CCMS)

ABSTRACT Chitosan and capsaicin are compounds extracted from natural products and have been indicated to lower body weight and prevent fatty liver. However, their applications are limited by poor oral bioavailability, low compliance and some serious side effects. To solve these problems, we successfully prepared chitosan microspheres (CTMS) and chitosan-capsaicin microspheres (CCMS) in previous study. Therefore, in the present study, we evaluated the ability of CTMS and CCMS to eliminate lipid accumulation in hepatocytesand also characterized their pharmacokinetic parameters after administration. The results showed that the two microspheres could significantly reduce intracellular lipid accumulation and dose-dependently improve the triglyceride (TG) content in HepG2 cells. A pharmacokinetic study indicated that CTMS and CCMS were distributed in almost all of the measured tissues, especially liver and kidney, and that their absorption was better than those of chitosan and capsaicin. Simultaneously, the prolonged circulating half-lives, the lower clearance and higher plasma concentration of CTMS and CCMS showed that their bioavailability was effectively enhanced. All of the results indicated that the lipid accumulation inhibition of CTMS and CCMS was better than that of chitosan and capsaicin, and that these microspheres can be developed as preventive agents for fatty liver or obesity.