Influence of castration-induced testosterone and estradiol deficiency on obesity and glucose metabolism in male Göttingen minipigs

Low testosterone and estradiol concentrations are predictive for the development of the metabolic syndrome in men and women, respectively. The aim of this study was to investigate the influence of sex hormone deficiency on food intake, body weight, body composition and glucose metabolism in male Göttingen minipigs.Five adult male Göttingen minipigs were studied before castration (pre-cast), 10-18 days (post-cast 1) and 10-11 weeks (post-cast 2) after castration. Parameters of interest were food intake, body weight, body fat percentage and sex hormone concentrations. Furthermore glucose tolerance, glucagon suppression, insulin resistance, beta cell function and disposition index were evaluated by oral and intravenous glucose tolerance tests.Castration led to almost complete disappearance of circulating testosterone and estradiol and secondarily to increased food intake, body weight and body fat percentage. Ten-eighteen days sex hormone deficiency (post-cast 1) did not significantly change any of the investigated metabolic parameters compared to pre-cast levels. Ten weeks after castration (post-cast 2) significant insulin resistance, glucose intolerance and hyperglucagonemia was found, and the beta cell function and the disposition index both were decreased.In conclusion, castration-induced sex hormone deficiency in male Göttingen minipigs results in hyperphagia, obesity and disturbed glucose metabolism, which are some of the features typical for the human metabolic syndrome.     

The obese Göttingen minipig as a model of the metabolic syndrome: dietary effects on obesity, insulin sensitivity, and growth hormone profile

The objective of the study reported here was to induce obesity in the female G?ttingen minipig to establish a model of the human metabolic syndrome. Nine- to ten-month-old female G?ttingen minipigs received a high-fat high-energy (HFE) diet or a low-fat, low-energy (LFE) diet. The energy contents derived from fat were 55 and 13 %, respectively. After 5 weeks, animals were subjected to dual energy x-ray absorptiometry (DEXA) scanning, intravenous glucose tolerance testing (IVGTT), and 6-h growth hormone profile recording. After treatment, mean body weight of pigs of the LFE group was 21.0 +/- 0.4 kg, and was 26.8 +/- 0.2 kg in pigs of the HFE group (P < 0.0001). The DEXA scanning indicated that the fat content of the LFE group was 10.0 +/- 1.2 % versus 15.2 +/- 0.7 % in the HFE group (P < 0.003). Triglycerides concentration was significantly (P < 0.05) increased in pigs of the HFE group (0.24 +/- 0.03 mM), compared with that in pigs of the LFE group (0.13 +/- 0.04 mM). Preprandial plasma glucose and insulin concentrations were not affected, but insulin area under the curve during IVGTT was significantly high in the obese animals. Growth hormone (GH) secretion was low in both groups of pigs. The obese minipig shares some of the metabolic impairments seen in obese humans, and may thus serve as a model of the metabolic syndrome.     

Extensive changes in innate immune gene expression in obese Göttingen minipigs do not lead to changes in concentrations of circulating cytokines and acute phase proteins

The usefulness of Göttingen minipigs as models for obesity and obesity‐related pathologies is well established. The low‐grade inflammation associated with obesity involves a range of innate immune factors; however, to our knowledge, the impact of obesity on innate immune factor expression has not been studied in Göttingen minipigs. Therefore, we studied the expression of innate immune genes in liver and adipose tissues as well as serum concentrations of cytokines and acute phase proteins in obese vs. lean Göttingen minipigs. In the liver, of 35 investigated genes, the expression of nine was significantly different in obese pigs (three up‐regulated, six down‐regulated). Of 33 genes in adipose tissues, obesity was associated with changed expression of 12 genes in the visceral adipose tissue (VAT) (three up‐regulated), 11 in the abdominal retroperitoneal adipose tissue (RPAT) (seven of these up‐regulated) and eight in the subcutaneous adipose tissue (SAT) from the neck (five of which were up‐regulated). Obesity‐associated expression changes were observed for three genes in all adipose tissues, namely chemokine (C‐C motif) ligand 3‐like 1 (up‐regulated), CD200 molecule (down‐regulated) and interleukin 1 receptor antagonist (up‐regulated) with interleukin 1 receptor antagonist being the most highly regulated gene in both VAT and RPAT. Looking at patterns of expression across the three types of adipose tissues, obesity was associated with an increased number of acute phase proteins differentially expressed between adipose tissues and a decreased tissue‐specific expression of cytokines and chemokines. In contrast to obese humans, no changes in serum concentrations of haptoglobin, C‐reactive protein, serum amyloid A, tumor necrosis factor‐α and interleukin 6 were found in obese Göttingen minipigs.     

Nicotinamide nucleotide transhydrogenase mRNA expression is related to human obesity

Objective:

A spontaneous deletion in the nicotinamide nucleotide transhydrogenase (Nnt) gene eliminating exons 7‐11 in C57BL/6J (B6J) mice is associated with reduced glucose‐stimulated insulin secretion in vitro, impaired glucose tolerance, higher epigonadal fat mass, and altered susceptibility to diet induced obesity of male B6J mice was proposed. A potential implication for NNT in human adipose tissue distribution has not been investigated so far.

Design and Methods:

Therefore, NNT mRNA expression in paired human samples of visceral (vis) and subcutaneous (sc) adipose tissue from 221 subjects with a wide range of body mass index (BMI), insulin sensitivity, and glucose tolerance was analyzed.

Results:

NNT mRNA expression is significantly higher in visceral fat of obese patients and correlates with body weight, BMI, % body fat, visceral and sc fat area, waist and hip circumference, and fasting plasma insulin (FPI). Multivariate linear regression analysis revealed visceral NNT expression as age and gender independent predictor of BMI, waist circumference, visceral fat area, and % body fat, but not FPI and 2 h OGTT glucose.

Conclusion:

In conclusion, a functional relevance of NNT in the development of human obesity and visceral fat distribution was suggested here.     

Energy Dense,Protein Restricted Diet Increases Adiposity and Perturbs Metabolism in Young,Genetically Lean Pigs

Animal models of obesity and metabolic dysregulation during growth (or childhood) are lacking. Our objective was to increase adiposity and induce metabolic syndrome in young, genetically lean pigs. Pre-pubertal female pigs, age 35 d, were fed a high-energy diet (HED; n = 12), containing 15% tallow, 35% refined sugars and 9.1–12.9% crude protein, or a control corn-based diet (n = 11) with 12.2–19.2% crude protein for 16 wk. Initially, HED pigs self-regulated energy intake similar to controls, but by wk 5, consumed more (P<0.001) energy per kg body weight. At wk 15, pigs were subjected to an oral glucose tolerance test (OGTT); blood glucose increased (P<0.05) in control pigs and returned to baseline levels within 60 min. HED pigs were hyperglycemic at time 0, and blood glucose did not return to baseline (P = 0.01), even 4 h post-challenge. During OGTT, glucose area under the curve (AUC) was higher and insulin AUC was lower in HED pigs compared to controls (P = 0.001). Chronic HED intake increased (P<0.05) subcutaneous, intramuscular, and perirenal fat deposition, and induced hyperglycemia, hypoinsulinemia, and low-density lipoprotein hypercholesterolemia. A subset of HED pigs (n = 7) was transitioned back to a control diet for an additional six weeks. These pigs were subjected to an additional OGTT at 22 wk. Glucose AUC and insulin AUC did not improve, supporting that dietary intervention was not sufficient to recover glucose tolerance or insulin production. These data suggest a HED may be used to increase adiposity and disrupt glucose homeostasis in young, growing pigs.     

Chronic consumption of farmed salmon containing persistent organic pollutants causes insulin resistance and obesity in mice

Background

Dietary interventions are critical in the prevention of metabolic diseases. Yet, the effects of fatty fish consumption on type 2 diabetes remain unclear. The aim of this study was to investigate whether a diet containing farmed salmon prevents or contributes to insulin resistance in mice.

Methodology/Principal Findings

Adult male C57BL/6J mice were fed control diet (C), a very high-fat diet without or with farmed Atlantic salmon fillet (VHF and VHF/S, respectively), and Western diet without or with farmed Atlantic salmon fillet (WD and WD/S, respectively). Other mice were fed VHF containing farmed salmon fillet with reduced concentrations of persistent organic pollutants (VHF/S_-POPs). We assessed body weight gain, fat mass, insulin sensitivity, glucose tolerance, ex vivo muscle glucose uptake, performed histology and immunohistochemistry analysis, and investigated gene and protein expression. In comparison with animals fed VHF and WD, consumption of both VHF/S and WD/S exaggerated insulin resistance, visceral obesity, and glucose intolerance. In addition, the ability of insulin to stimulate Akt phosphorylation and muscle glucose uptake was impaired in mice fed farmed salmon. Relative to VHF/S-fed mice, animals fed VHF/S_-POPs had less body burdens of POPs, accumulated less visceral fat, and had reduced mRNA levels of TNFα as well as macrophage infiltration in adipose tissue. VHF/S_-POPs-fed mice further exhibited better insulin sensitivity and glucose tolerance than mice fed VHF/S.

Conclusions/Significance

Our data indicate that intake of farmed salmon fillet contributes to several metabolic disorders linked to type 2 diabetes and obesity, and suggest a role of POPs in these deleterious effects. Overall, these findings may participate to improve nutritional strategies for the prevention and therapy of insulin resistance.     

Associations between Ultrasound Measures of Abdominal Fat Distribution and Indices of Glucose Metabolism in a Population at High Risk of Type 2 Diabetes: The ADDITION-PRO Study

Aims

Visceral adipose tissue measured by CT or MRI is strongly associated with an adverse metabolic risk profile. We assessed whether similar associations can be found with ultrasonography, by quantifying the strength of the relationship between different measures of obesity and indices of glucose metabolism in a population at high risk of type 2 diabetes.

Methods

A cross-sectional analysis of 1342 participants of the ADDITION-PRO study. We measured visceral adipose tissue and subcutaneous adipose tissue with ultrasonography, anthropometrics and body fat percentage by bioelectrical impedance. Indices of glucose metabolism were derived from a three point oral glucose tolerance test. Linear regression of obesity measures on indices of glucose metabolism was performed.

Results

Mean age was 66.2 years, BMI 26.9kg/m², subcutaneous adipose tissue 2.5cm and visceral adipose tissue 8.0cm. All measures of obesity were positively associated with indicators of glycaemia and inversely associated with indicators of insulin sensitivity. Associations were of equivalent magnitude except for subcutaneous adipose tissue and the visceral/subcutaneous adipose tissue ratio, which showed weaker associations. One standard deviation difference in BMI, visceral adipose tissue, waist circumference, waist/height ratio and body fat percentage corresponded approximately to 0.2mmol/l higher fasting glucose, 0.7mmol/l higher 2-hr glucose, 0.06-0.1% higher HbA1c, 30 % lower HOMA index of insulin sensitivity, 20% lower Gutt’s index of insulin sensitivity, and 100 unit higher Stumvoll’s index of beta-cell function. After adjustment for waist circumference visceral adipose tissue was still significantly associated with glucose intolerance and insulin resistance, whereas there was a trend towards inverse or no associations with subcutaneous adipose tissue. After adjustment, a 1cm increase in visceral adipose tissue was associated with ~5% lower insulin sensitivity (p≤0.0004) and ~0.18mmol/l higher 2-hr glucose (p≤0.001).

Conclusion

Visceral and subcutaneous adipose tissue assessed by ultrasonography are significantly associated with glucose metabolism, even after adjustment for other measures of obesity.     

Gender-associated differences in metabolic syndrome-related parameters in Göttingen minipigs

Gender-associated differences in pathophysiology and treatment of disease are an evolving area in human medicine that should be addressed in animal models. The aim of this study was to characterize gender differences in metabolic parameters of G?ttingen minipigs and to determine which gender has the metabolic profile that is most appropriate as a model for human metabolic syndrome. Blood samples were collected from fasted, lean male and female G?ttingen minipigs at 8 wk and 8 mo of age. Samples were analyzed for glucose, fructosamine, insulin, C-peptide, glucagon, triglycerides, total cholesterol, high-density lipoprotein cholesterol (HDL-c), free fatty acids, leptin, testosterone, and 17beta-estradiol. Insulin sensitivity and beta cell function were estimated by homeostasis model assessment and degree of obesity by measuring the abdominal circumference. Male minipigs had higher concentrations of both testosterone and estradiol. Female minipigs had a larger abdominal circumference and higher concentrations of C-peptide, insulin, triglyceride, total cholesterol, HDL-c and leptin but a lower concentration of free fatty acids and lower HDL-c:total cholesterol ratio. Compared with male minipigs, female minipigs were more insulin-resistant and had a higher beta-cell function. No gender-associated differences were found in any of the other investigated parameters. In conclusion, female minipigs were more obese and insulin-resistant and had a more atherogenic plasma profile than did their male counterparts and therefore may be better models for metabolic syndrome. Their high concentrations of both testosterone and estradiol may protect male minipigs from obesity and metabolic disturbances.     

Characterisation of Gut Microbiota in Ossabaw and G?ttingen Minipigs as Models of Obesity and Metabolic Syndrome

Background

Recent evidence suggests that the gut microbiota is an important contributing factor to obesity and obesity related metabolic disorders, known as the metabolic syndrome. The aim of this study was to characterise the intestinal microbiota in two pig models of obesity namely Göttingen minipigs and the Ossabaw minipigs.

Methods and Findings

The cecal, ileal and colonic microbiota from lean and obese Osabaw and Göttingen minipigs were investigated by Illumina-based sequencing and by high throughput qPCR, targeting the 16S rRNA gene in different phylogenetic groups of bacteria. The weight gain through the study was significant in obese Göttingen and Ossabaw minipigs. The lean Göttingen minipigs’ cecal microbiota contained significantly higher abundance of Firmicutes (P<0.006), Akkermensia (P<0.01) and Methanovibribacter (P<0.01) than obese Göttingen minipigs. The obese Göttingen cecum had higher abundances of the phyla Spirochaetes (P<0.03), Tenericutes (P<0.004), Verrucomicrobia (P<0.005) and the genus Bacteroides (P<0.001) compared to lean minipigs. The relative proportion of Clostridium cluster XIV was 7.6-fold higher in cecal microbiota of obese Göttingen minipigs as compared to lean. Obese Ossabaw minipigs had a higher abundance of Firmicutes in terminal ileum and lower abundance of Bacteroidetes in colon than lean Ossabaw minipigs (P<0.01). Obese Ossabaws had significantly lower abundances of the genera Prevotella and Lactobacillus and higher abundance of Clostridium in their colon than the lean Ossabaws. Overall, the Göttingen and Ossabaw minipigs displayed different microbial communities in response to diet-induced obesity in the different sections of their intestine.

Conclusion

Obesity-related changes in the composition of the gut microbiota were found in lean versus obese Göttingen and Ossabaw minipigs. In both pig models diet seems to be the defining factor that shapes the gut microbiota as observed by changes in different bacteria divisions between lean and obese minipigs.     

Oral Glucose Tolerance is Associated with Neuroelectric Indices of Attention Among Adults with Overweight and Obesity

Objective

This study aimed to elucidate the relationship between glucose levels and insulin resistance and sensitivity obtained from oral glucose tolerance tests and neurophysiological indices of attention among adults with overweight and obesity.

Methods

Forty adults with overweight or obesity (BMI ≥ 25 kg/m²) underwent dual‐energy x‐ray absorptiometry to assess visceral adipose tissue. Repeated venous blood samples were collected during an oral glucose tolerance test to measure insulin resistance (homeostatic model assessment of insulin resistance) and indices of insulin sensitivity (Matsuda index and Stumvoll metabolic clearance rate). Attention was assessed using event‐related brain potentials recorded during a visual oddball task. Amplitude and latency of the P3 wave form in a central‐parietal region of interest were used to index attentional resource allocation and information processing speed.

Results

Following adjustment for visceral adipose tissue, reduced values of Matsuda index and Stumvoll metabolic clearance rate (indicating poor insulin sensitivity) were correlated with longer peak latency, whereas insulin area under the curve was positively related to peak latency, indicating slower information processing. Individuals with decreased insulin sensitivity (Matsuda index < 4.3) had significantly longer P3 latencies compared with individuals with normal insulin sensitivity.

Conclusions

Higher fasting glucose, but not homeostatic model assessment of insulin resistance, and reduced indices of glucose sensivity are associated with decrements in attention characterized by slower reaction time and slower information processing speed among adults with overweight and obesity.

     

Components of metabolic syndrome and coronary artery disease in female Ossabaw swine fed excess atherogenic diet

Ossabaw swine have a 'thrifty genotype' (propensity to obesity) that enables them to survive seasonal food shortages in their native environment. Consumption of excess kcal causes animals of the thrifty genotype to manifest components of the metabolic syndrome, including central (intra-abdominal) obesity, insulin resistance, impaired glucose tolerance, dyslipidemia, and hypertension. We determined whether female Ossabaw swine manifest multiple components of the metabolic syndrome by comparing lean pigs fed a normal maintenance diet (7% kcal from fat; lean, n = 9) or excess chow with 45% kcal from fat and 2% cholesterol (obese, n = 8). After 9 wk, body composition, glucose tolerance, plasma lipids, and intravascular ultrasonography and histopathology of coronary arteries were assessed. Computed tomography (CT) assessed subcutaneous and intra-abdominal fat deposition and was compared with traditional methods, including anatomical measurements, backfat ultrasonography, and proximate chemical composition analysis. Compared with lean animals, obese swine showed 2-fold greater product of the plasma insulin x glucose concentrations, 4.1-fold greater total cholesterol, 1.6-fold greater postprandial triglycerides, 4.6-fold greater low- to high-density lipoprotein cholesterol ratio, hypertension, and neointimal hyperplasia of coronary arteries. The 1.5-fold greater body weight in obese swine was largely accounted for by the 3-fold greater carcass fat mass. High correlation (0.79 to 0.95) of CT, anatomical measurements, and ultrasonography with direct chemical measures of subcutaneous, retroperitoneal, and visceral fat indicates high validity of all indirect methods. We conclude that relatively brief feeding of excess atherogenic diet produces striking features of metabolic syndrome and coronary artery disease in female Ossabaw swine.     

Dietary supplementation with Agaricus blazei murill extract prevents diet‐induced obesity and insulin resistance in rats

Objective:

Dietary supplement may potentially help to fight obesity and other metabolic disorders such as insulin‐resistance and low‐grade inflammation. The present study aimed to test whether supplementation with Agaricus blazei murill (ABM) extract could have an effect on diet‐induced obesity in rats.

Design and Methods:

Wistar rats were fed with control diet (CD) or high‐fat diet (HF) and either with or without supplemented ABM for 20 weeks.

Results:

HF diet‐induced body weight gain and increased fat mass compared to CD. In addition HF‐fed rats developed hyperleptinemia and insulinemia as well as insulin resistance and glucose intolerance. In HF‐fed rats, visceral adipose tissue also expressed biomarkers of inflammation. ABM supplementation in HF rats had a protective effect against body weight gain and all study related disorders. This was not due to decreased food intake which remained significantly higher in HF rats whether supplemented with ABM or not compared to control. There was also no change in gut microbiota composition in HF supplemented with ABM. Interestingly, ABM supplementation induced an increase in both energy expenditure and locomotor activity which could partially explain its protective effect against diet‐induced obesity. In addition a decrease in pancreatic lipase activity is also observed in jejunum of ABM‐treated rats suggesting a decrease in lipid absorption.

Conclusions:

Taken together these data highlight a role for ABM to prevent body weight gain and related disorders in peripheral targets independently of effect in food intake in central nervous system.     

Enhanced Lipid Oxidation and Maintenance of Muscle Insulin Sensitivity Despite Glucose Intolerance in a Diet-Induced Obesity Mouse Model

Background

Diet-induced obesity is a rising health concern which can lead to the development of glucose intolerance and muscle insulin resistance and, ultimately, type II diabetes mellitus. This research investigates the associations between glucose intolerance or muscle insulin resistance and tissue specific changes during the progression of diet-induced obesity.

Methodology

C57BL/6J mice were fed a normal or high-fat diet (HFD; 60% kcal fat) for 3 or 8 weeks. Disease progression was monitored by measurements of body/tissue mass changes, glucose and insulin tolerance tests, and ex vivo glucose uptake in intact muscles. Lipid metabolism was analyzed using metabolic chambers and ex vivo palmitate assays in intact muscles. Skeletal muscle, liver and adipose tissues were analyzed for changes in inflammatory gene expression. Plasma was analyzed for insulin levels and inflammatory proteins. Histological techniques were used on muscle and liver cryosections to assess metabolic and morphological changes.

Principal Findings/Conclusions

A rapid shift in whole body metabolism towards lipids was observed with HFD. Following 3 weeks of HFD, elevated total lipid oxidation and an oxidative fiber type shift had occurred in the skeletal muscle, which we propose was responsible for delaying intramyocellular lipid accumulation and maintaining muscle’s insulin sensitivity. Glucose intolerance was present after three weeks of HFD and was associated with an enlarged adipose tissue depot, adipose tissue inflammation and excess hepatic lipids, but not hepatic inflammation. Furthermore, HFD did not significantly increase systemic or muscle inflammation after 3 or 8 weeks of HFD suggesting that early diet-induced obesity does not cause inflammation throughout the whole body. Overall these findings indicate skeletal muscle did not contribute to the development of HFD-induced impairments in whole-body glucose tolerance following 3 weeks of HFD.     

Sucrose counteracts the anti-inflammatory effect of fish oil in adipose tissue and increases obesity development in mice

Background

Polyunsaturated n-3 fatty acids (n-3 PUFAs) are reported to protect against high fat diet-induced obesity and inflammation in adipose tissue. Here we aimed to investigate if the amount of sucrose in the background diet influences the ability of n-3 PUFAs to protect against diet-induced obesity, adipose tissue inflammation and glucose intolerance.

Methodology/Principal Findings

We fed C57BL/6J mice a protein- (casein) or sucrose-based high fat diet supplemented with fish oil or corn oil for 9 weeks. Irrespective of the fatty acid source, mice fed diets rich in sucrose became obese whereas mice fed high protein diets remained lean. Inclusion of sucrose in the diet also counteracted the well-known anti-inflammatory effect of fish oil in adipose tissue, but did not impair the ability of fish oil to prevent accumulation of fat in the liver. Calculation of HOMA-IR indicated that mice fed high levels of proteins remained insulin sensitive, whereas insulin sensitivity was reduced in the obese mice fed sucrose irrespectively of the fat source. We show that a high fat diet decreased glucose tolerance in the mice independently of both obesity and dietary levels of n-3 PUFAs and sucrose. Of note, increasing the protein∶sucrose ratio in high fat diets decreased energy efficiency irrespective of fat source. This was accompanied by increased expression of Ppargc1a (peroxisome proliferator-activated receptor, gamma, coactivator 1 alpha) and increased gluconeogenesis in the fed state.

Conclusions/Significance

The background diet influence the ability of n-3 PUFAs to protect against development of obesity, glucose intolerance and adipose tissue inflammation. High levels of dietary sucrose counteract the anti-inflammatory effect of fish oil in adipose tissue and increases obesity development in mice.     

Effects of Visceral Fat and Weight Loss on Lipoprotein(a) Concentration in Subjects with Obesity

ZAMBONI M, R FACCHINETTI, F ARMELLINI, E TURCATO, IA BERGAMO ANDREIS, O BOSELLO. Effects of visceral fat and weight loss on lipoprotein(a) concentration in subjects with obesity. We studied the relationships between regional body fat distribution and metabolic variables with lipoprotein(a) [Lp(a)] as well as the effects of weight loss on Lp(a) in 25 women and 9 men with obesity. Regional body fat distribution, as evaluated by the use of computed tomography; Lp(a); and fasting glucose, insulin, cholesterol, and triglycerides were analyzed before and after a very low-energy diet. No significant correlations were found between visceral, subcutaneous, and total fat and Lp(a) or between metabolic variables and Lp(a). All anthropometric variables significantly decreased after a very low-energy diet. Fasting glucose, insulin, triglycerides, and cholesterol significantly decreased after a very low-energy diet. No significant changes in Lp(a) concentration after a very low-energy diet were found. The correlation between the initial values of Lp(a) and changes of Lp(a) after a very low-energy diet was slightly significant (ρ=0.33, p<0.06). In conclusion, our study shows that Lp(a) is not influenced by obesity, visceral fat, metabolic variables, or weight loss induced by a very low-energy diet     

Growth differences of male and female Göttingen minipigs during ad libitum feeding: a pilot study

Even though minipigs have been used in biomedical research for nearly half a century now, no specific nutrient requirements are available. For that reason a series of studies into the nutrient requirements of G?ttingen minipigs were carried out. Firstly, a pilot study was carried out to determine the ad libitum feed intake (FI) during growth, as a reference for later feed restriction studies. Four male and four female minipigs were fed two types of diet, one standard pig diet (20.6% crude protein; 11.7% crude fat; 13.5 mJ/kg DM metabolizable energy) and one diet specially designed for minipigs (12.0% crude protein; 2.9% crude fat; 11.9 MJ/kg DM metabolizable energy). When fed ad libitum for 13 weeks, female G?ttingen minipigs developed a significantly (P<0.05) higher body weight (BW) than males (27.4 vs 16.6 kg) on either diet. The large difference in growth between male and female G?ttingen minipigs did not appear to be the result from differences in metabolizable energy intake. Metabolizable energy intake of male and female G?ttingen minipigs could be predicted by ME=1877 kJxBW(0.61). Both male and female G?ttingen minipigs became obese when fed ad libitum, defined by relative backfat thickness. Relative backfat thickness ranged from 5 to 13 cm/100 kg. Females had thicker relative backfat layers than males. Remarkably, no large changes in haematology and clinical chemistry occurred in ad libitum fed G?ttingen minipigs as compared to reference values, and no abnormalities other than enlarged fat reserves were observed at necropsy. Apparently, G?ttingen minipigs do not restrain FI voluntarily, and restricted feeding is therefore indicated to prevent obesity.     

Subcutaneous lipectomy causes a metabolic syndrome in hamsters

The insulin resistance syndrome X is related to excess intra-abdominal adipose tissue. With lipectomy of >50% of subcutaneous adipose tissue (SQAT) in nonhibernating, adult female Syrian hamsters on high-fat (HF; 50 calorie%) diet and measurements of oral glucose tolerance, oral [(14)C]oleic acid disposal, serum triglycerides, serum leptin, liver fat, perirenal (PR) adipose tissue cellularity, and body composition, we studied the role of SQAT. Sham-operated (S) animals on HF or low-fat (LF; 12.5 calorie%) diets served as controls. After 3 mo there was no visible regrowth of SQAT but HF diet led to similar levels of body weight and body fat in lipectomized and sham-operated animals. Lipectomized (L) animals had more intra-abdominal fat as a percentage of total body fat, higher insulinemic index, a strong trend toward increased liver fat content, and markedly elevated serum triglycerides compared with S-HF and S-LF. Liver and PR adipose tissue uptake of fatty acid were similar in L-HF and S-HF but reduced vs. S-LF, and were inversely correlated with liver fat content and insulin sums during the oral glucose tolerance test. In summary, lipectomy of SQAT led to compensatory fat accumulation implying regulation of total body fat mass. In conjunction with HF diet these lipectomized hamsters developed a metabolic syndrome with significant hypertriglyceridemia, relative increase in intra-abdominal fat, and insulin resistance. We propose that SQAT, via disposal and storage of excess ingested energy, acts as a metabolic sink and protects against the metabolic syndrome of obesity.     

Vaspin gene expression in human adipose tissue: association with obesity and type 2 diabetes

Recently, vaspin was identified as an adipokine with insulin-sensitizing effects, which is predominantly secreted from visceral adipose tissue in a rat model of type 2 diabetes. In this study, we examined whether vaspin mRNA expression is a marker of visceral obesity and correlates with anthropometric and metabolic parameters in paired samples of visceral and subcutaneous adipose tissue from 196 subjects with a wide range of obesity, body fat distribution, insulin sensitivity, and glucose tolerance. Vaspin mRNA expression was only detectable in 23% of the visceral and in 15% of the subcutaneous (SC) adipose tissue samples. Vaspin mRNA expression was not detectable in lean subjects (BMI<25) and was more frequently detected in patients with type 2 diabetes. No significant correlations were found between visceral vaspin gene expression and visceral fat area or SC vaspin expression. However, visceral vaspin expression significantly correlates with BMI, % body fat, and 2 h OGTT plasma glucose. Subcutaneous vaspin mRNA expression is significantly correlated with WHR, fasting plasma insulin concentration, and glucose infusion rate during steady state of an euglycemic-hyperinsulinemic clamp. Multivariate linear regression analysis revealed % body fat as strongest predictor of visceral vaspin and insulin sensitivity as strongest determinant of SC vaspin mRNA expression. In conclusion, our data indicate that induction of human vaspin mRNA expression in adipose tissue is regulated in a fat depot-specific manner and could be associated with parameters of obesity, insulin resistance, and glucose metabolism.     

Critical role of Kupffer cells in the management of diet-induced diabetes and obesity

The aim of this study was to investigate the role of Kupffer cell in glucose metabolism and hepatic insulin sensitivity in mice. Both phagocytic activity and secretory capacity of Kupffer cells were blunted 24 h after GdCl₃ administration. Glucose tolerance - evaluated following an oral glucose tolerance test (OGTT) - was higher in GdCl₃-treated mice whereas fasting insulinemia and HOMA-IR index decreased. The improvement of glucose tolerance and hepatic insulin signalling pathway after inhibition of Kupffer cells was supported by a lower hepatic gluconeogenic enzyme expression and a higher phosphorylation of Akt upon insulin challenge. Moreover, fasting hyperglycemia, insulin resistance and impaired glucose tolerance - induced by high fat (HF) diet - were improved through chronic administration of GdCl₃. Interestingly, the inhibition of Kupffer cell exerted antiobesity effects in HF-fed mice, and lowered hepatic steatosis. Therefore, strategies targeting Kupffer cell functions could be a promising approach to counteract obesity and related metabolic disorders.     

Topical application of capsaicin reduces visceral adipose fat by affecting adipokine levels in high‐fat diet‐induced obese mice

Objective:

Visceral obesity contributes to the development of obesity‐related disorders such as diabetes, hyperlipidemia, and fatty liver disease, as well as cardiovascular diseases. In this study, we determined whether topical application of capsaicin can reduce fat accumulation in visceral adipose tissues.

Methods and Results:

We first observed that topical application of 0.075% capsaicin to male mice fed a high‐fat diet significantly reduced weight gain and visceral fat. Fat cells were markedly smaller in the mesenteric and epididymal adipose tissues of mice treated with capsaicin cream. The capsaicin treatment also lowered serum levels of fasting glucose, total cholesterol, and triglycerides. Immunoblot analysis and RT‐PCR revealed increased expression of adiponectin and other adipokines including peroxisome proliferator‐activated receptor (PPAR) α, PPARγ, visfatin, and adipsin, but reduced expression of tumor necrosis factor‐α and IL‐6.

Conclusions:

These results indicate that topical application of capsaicin to obese mice limits fat accumulation in adipose tissues and may reduce inflammation and increase insulin sensitivity.