Obesity Abstracts 1

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Body fat distribution, incident cardiovascular disease, cancer, and all-cause mortality.
            (Britton et al., 2013) Download
OBJECTIVES: The aim of this study was to determine whether ectopic fat depots are prospectively associated with cardiovascular disease, cancer, and all-cause mortality. BACKGROUND: The morbidity associated with excess body weight varies among individuals of similar body mass index. Ectopic fat depots may underlie this risk differential. However, prospective studies of directly measured fat are limited. METHODS: Participants from the Framingham Heart Study (n = 3,086; 49% women; mean age of 50.2 years) underwent assessment of fat depots (visceral adipose tissue, pericardial adipose tissue, and periaortic adipose tissue) using multidetector computed tomography and were followed up longitudinally for a median of 5.0 years. Cox proportional hazards regression models were used to examine the association of each fat depot (per 1 SD increment) with the risk of incident cardiovascular disease, cancer, and all-cause mortality after adjustment for standard risk factors, including body mass index. RESULTS: Overall, there were 90 cardiovascular events, 141 cancer events, and 71 deaths. After multivariable adjustment, visceral adipose tissue was associated with cardiovascular disease (hazard ratio: 1.44; 95% confidence interval: 1.08 to 1.92; p = 0.01) and cancer (hazard ratio: 1.43; 95% confidence interval: 1.12 to 1.84; p = 0.005). Addition of visceral adipose tissue to a multivariable model that included body mass index modestly improved cardiovascular risk prediction (net reclassification improvement of 16.3%). None of the fat depots were associated with all-cause mortality. CONCLUSIONS: Visceral adiposity is associated with incident cardiovascular disease and cancer after adjustment for clinical risk factors and generalized adiposity. These findings support the growing appreciation of a pathogenic role of ectopic fat.


 

Hormonal regulation of malic enzyme and glucose-6-phosphate dehydrogenase in brown adipose tissue.
            (Carvalho et al., 1993) Download
The activities of malic enzyme (ME) and glucose-6-phosphate dehydrogenase (G-6-PDH), two NADPH-generating lipogenic enzymes, were measured in brown adipose tissue (BAT) of rats undergoing various neurohormonal manipulations. Methimazole-induced hypothyroidism doubled the activity of these two enzymes but, surprisingly, triiodothyronine (T3) given to hypothyroid rats caused a time- and dose-dependent stimulation of up to three- to fourfold. Unilateral BAT denervation modestly reduced the activity of these enzymes (approximately 30%) and failed to prevent the stimulation induced by hypothyroidism, whereas growth hormone (GH) successfully blocked this effect of hypothyroidism. Insulin stimulated both enzymes regardless of the thyroid status but failed to abolish the inhibitory effect of GH. In intact rats, cold exposure caused a time-dependent increase in the activity of both ME and G-6-PDH, which reached 5.2- and 3-fold, respectively, after 96 h. This cold-induced stimulation was not observed in hypothyroid rats, but it was restored by physiological doses of thyroxine (800 ng.100 g body wt-1.24 h-1). Replacement with T3 (300 ng.100 g body wt-1.24 h-1), in contrast, did not have this effect. In hypothyroid rats with hemidenervation of BAT, norepinephrine (NE) modestly increased ME and G-6-PDH activities in the denervated side, with little or no effect in the intact side. Receptor-saturating doses of T3 (50 micrograms.100 g body wt-1.day-1 over 48 h) stimulated two- and threefold both enzymes in both sides, reducing or obliterating the effect of denervation. The data suggest a complex neurohormonal regulation of the activity of ME and G-6-PDH in BAT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adiponectin expression in subcutaneous adipose tissue is reduced in women with cellulite.
            (Emanuele et al., 2011) Download
BACKGROUND: Cellulite, which appears as orange peel-type or cottage cheese-like dimpling of the skin on the thighs and buttocks, is a complex, multifactorial, cosmetic disorder of the subcutaneous fat layer and the overlying superficial skin. Adiponectin is an adipocyte-derived hormone mainly produced by subcutaneous fat that shows important protective anti-inflammatory and vasodilatory effects. We hypothesized that adiponectin expressed in the subcutaneous adipose tissue (SAT) might play a role in the pathogenesis of cellulite. We reasoned that a reduction in the expression of adiponectin - a humoral vasodilator - in the SAT of cellulite areas might contribute to the altered microcirculation frequently found in these regions. METHODS: A total of 15 lean (body mass index [BMI] < 25 kg/m(2) ) women with cellulite and 15 age- and BMI-matched women without cellulite participated in this study. Real-time reverse transcription polymerase chain reaction (RT-PCR) was used to assess adiponectin gene expression. Plasma adiponectin levels were measured using a commercial enzyme immunoassay kit. RESULTS: Adiponectin mRNA expression in the SAT of the gluteal region was significantly lower in areas with cellulite compared with those without (12.6 +/- 3.1 AU versus 16.6 +/- 4.1 AU; P=0.006). However, plasma adiponectin levels did not differ between women with (20.3 +/- 7.3 mug/ml) and without (19.3 +/- 6.1 mug/ml) cellulite (P=0.69). CONCLUSIONS: Adiponectin expression is significantly reduced in the SAT in areas affected by cellulite. Our findings provide novel insights into the nature of cellulite and may give clues to the treatment of this cosmetic issue.

Appetite suppressive effects of yeast hydrolysate on nitric oxide synthase (NOS) expression and vasoactive intestinal peptide (VIP) immunoreactivity in hypothalamus.
            (Jung et al., 2008) Download
To investigate the effects of yeast hydrolysate on appetite regulation mechanisms in the central nervous system, nitric oxide synthase (NOS) expression and vasoactive intestinal peptide (VIP) immunoreactivity in the paraventricular nucleus (PVN) and ventromedial hypothalamic nucleus (VMH) of the hypothalamus were examined. Male Sprague-Dawley (SD) rats were assigned to five groups: control (normal diet), BY-1 and BY-2 (normal diet with oral administration of 0.1 g and 1.0 g of yeast hydrolysate <10 kDa/kg body weight, respectively), AY-1 and AY-2 (normal diet with oral administration of 0.1 g and 1.0 g of yeast hydrolysate 10-30 kDa/kg body weight, respectively). The body weight gain in the BY groups was less than that in the control. In particular, the weight gain of the BY-2 group (133.0 +/- 5.1 g) was significantly lower (p < 0.05) than that of the control group (150.1 +/- 3.7 g). Among the test groups, the BY-2 group was shown to have significantly lower triacylglycerol (TG) levels (p < 0.05) than the other groups. The staining intensities and optical densities of NOS neurons in the PVN of the AY group were significantly higher (p < 0.05) than in the control and BY groups. The staining intensities and optical densities of VIP immunoreactivity in the PVN and VMH of the BY groups were higher than those of the AY groups and the control. In conclusion, these results indicated that yeast hydrolysate of <10 kDa reduced the body weight gain and body fat in normal diet-fed rats and increased the lipid energy metabolism by altering the expression of NOS and VIP in neurons.


 

Effects of yeast hydrolysate on hepatic lipid metabolism in high-fat-diet-induced obese mice: yeast hydrolysate suppresses body fat accumulation by attenuating fatty acid synthesis.
            (Jung et al., 2012) Download
AIMS: We observed whether the anti-obesity activity of yeast hydrolysate (YH) was due to the alteration of lipid-regulating enzyme activities. METHODS: Male ICR mice were divided into four groups: a normal diet group (ND; 4.2% fat), a high-fat diet group (HF; 27.7% fat), an HF group treated orally with 0.5% or 1% YH in the drinking water (HF+YH0.5; 27.7% fat and HF+YH1; 27.7% fat). RESULTS: After 5 weeks, the YH groups (HF+YH0.5=3.92+/-0.17 g/100 g BW and HF+YH1=3.76+/-0.13 g/100 g BW) had significantly lower levels of epididymal fats compared to the HF group (4.91+/-0.29 g/100 g BW; p<0.05). YH supplementation produced a decrease in serum triglycerides and low-density lipoprotein cholesterol concentrations and body weight gain, and produced a dose-dependent significant increase in serum ghrelin compared with the HF group (p<0.05). Hepatic glucose-6-phosphate dehydrogenase (G6PD) activity was inhibited by YH supplementation compared with the HF group, and mice treated orally with 1% YH exhibited a significant decrease in hepatic malic enzyme (ME) activity compared to obese mice treated with the vehicle (HF=10.44+/-2.74 nmol/min/mg protein vs. HF+YH1=6.68+/-2.23 nmol/min/mg protein; p<0.05). CONCLUSIONS: YH supplementation suppressed body fat accumulation by attenuating fatty acid synthesis through the downregulation of hepatic G6PD and ME activities.

Yeast hydrolysate can reduce body weight and abdominal fat accumulation in obese adults.
            (Jung et al., 2014) Download
OBJECTIVE: The aim of this study was to examine the effect of yeast hydrolysate on the abdominal fat in obese humans. METHODS: We observed the effects of yeast hydrolysate that had a molecular weight below 10 kDa on the anti-abdominal fat accumulation in obese men and women ages 20 to 50 y for 10 wk. The abdominal fat mass was assessed by computed tomographic scans. RESULTS: By the sixth week, the reductions in energy intake in the yeast group (yeast hydrolysate 1 g/d) were significantly greater than those in the control group (placebo 1 g/d) (P < 0.05). The body weight and body mass index (BMI) were significantly reduced by week 10 compared with baseline in the yeast group, and these differences were significantly greater than those in the control group: body weight 0.83 kg versus -2.60 k g (P < 0.001), BMI 0.29 kg/m(2) versus -0.90 kg/m(2) (P < 0.001). Despite the increased loss of body weight in the yeast group, lean body mass did not significantly differ between the two groups. Body fat mass in the control group did not significantly change between baseline and week 10. However, the yeast group lost a significant amount of body fat mass after 10 wk of treatment (P < 0.01). The differences in abdominal fat thickness and abdominal circumference between the two groups were significant after 10 wk of treatment (P < 0.001). The total abdominal fat area in the yeast group was significantly lower than in the control group after 10 wk of treatment (-7.06 cm(2) versus -17.34 cm(2); P < 0.01). CONCLUSIONS: Yeast hydrolysate can reduce body weight and the accumulation of abdominal fat without an adverse effect on lean body mass in obese adults, regardless of sex, via the reduction of energy intake.

Role of adipokines and cytokines in obesity-associated breast cancer: therapeutic targets.
            (Khan et al., 2013) Download
Obesity is the cause of a large proportion of breast cancer incidences and mortality in post-menopausal women. In obese people, elevated levels of various growth factors such as insulin and insulin-like growth factors (IGFs) are found. Elevated insulin level leads to increased secretion of estrogen by binding to the circulating sex hormone binding globulin (SHBG). The increased estrogen-mediated downstream signaling favors breast carcinogenesis. Obesity leads to altered expression profiles of various adipokines and cytokines including leptin, adiponectin, IL-6, TNF-alpha and IL-1beta. The increased levels of leptin and decreased adiponectin secretion are directly associated with breast cancer development. Increased levels of pro-inflammatory cytokines within the tumor microenvironment promote tumor development. Efficacy of available breast cancer drugs against obesity-associated breast cancer is yet to be confirmed. In this review, we will discuss different adipokine- and cytokine-mediated molecular signaling pathways involved in obesity-associated breast cancer, available therapeutic strategies and potential therapeutic targets for obesity-associated breast cancer.

Increasing adiposity: consequence or cause of overeating?
            (Ludwig and Friedman, 2014) Download

Associations between adipokines and obesity-related cancer.
            (Paz-Filho et al., 2011) Download
There is increasing evidence that obesity may have pathophysiological effects that extend beyond its well-known co-morbidities; in particular its role in cancer has received considerable epidemiological support. As adipose tissue becomes strongly established as an endocrine organ, two of its most abundant and most investigated adipokines, leptin and adiponectin, are also taken beyond their traditional roles in energy homeostasis, and are implicated as mediators of the effects of obesity on cancer development. This review examines these adipokines in relation to the prostate, breast, colorectal, thyroid, renal, pancreatic, endometrial and oesophageal cancers, and how they may orchestrate the influence of obesity on the development of these malignancies.

The microbiome and obesity: is obesity linked to our gut flora?
            (Tsai and Coyle, 2009) Download
The human gut is a lush microbial ecosystem containing about 100 trillion microorganisms, whose collective genome, the microbiome, contains 100-fold more genes than the entire human genome. The symbiosis of our extended genome plays a role in host homeostasis and energy extraction from diet. In this article, we summarize some of the studies that have advanced the understanding of the microbiome and its effects on metabolism, obesity, and health. Metagenomic studies demonstrated that certain mixes of gut microbiota may protect or predispose the host to obesity. Furthermore, microbiota transplantation studies in germ-free murine models showed that the efficient energy extraction traits of obese-type gut flora are transmissible. The proposed methods by which the microbiome may contribute to obesity include increasing dietary energy harvest, promoting fat deposition, and triggering systemic inflammation. Future treatments for obesity may involve modulation of gut microbiota using probiotics or prebiotics.


References

Britton, KA, et al. (2013), ‘Body fat distribution, incident cardiovascular disease, cancer, and all-cause mortality.’, J Am Coll Cardiol, 62 (10), 921-25. PubMedID: 23850922
Carvalho, SD, N Negrao, and AC Bianco (1993), ‘Hormonal regulation of malic enzyme and glucose-6-phosphate dehydrogenase in brown adipose tissue.’, Am J Physiol, 264 (6 Pt 1), E874-81. PubMedID: 8333512
Emanuele, E, et al. (2011), ‘Adiponectin expression in subcutaneous adipose tissue is reduced in women with cellulite.’, Int J Dermatol, 50 (4), 412-16. PubMedID: 21413950
Jung, EY, et al. (2008), ‘Appetite suppressive effects of yeast hydrolysate on nitric oxide synthase (NOS) expression and vasoactive intestinal peptide (VIP) immunoreactivity in hypothalamus.’, Phytother Res, 22 (11), 1417-22. PubMedID: 18972585
Jung, EY, et al. (2012), ‘Effects of yeast hydrolysate on hepatic lipid metabolism in high-fat-diet-induced obese mice: yeast hydrolysate suppresses body fat accumulation by attenuating fatty acid synthesis.’, Ann Nutr Metab, 61 (2), 89-94. PubMedID: 22889874
Jung, EY, et al. (2014), ‘Yeast hydrolysate can reduce body weight and abdominal fat accumulation in obese adults.’, Nutrition, 30 (1), 25-32. PubMedID: 24290594
Khan, S, et al. (2013), ‘Role of adipokines and cytokines in obesity-associated breast cancer: therapeutic targets.’, Cytokine Growth Factor Rev, 24 (6), 503-13. PubMedID: 24210902
Ludwig, DS and MI Friedman (2014), ‘Increasing adiposity: consequence or cause of overeating?’, JAMA, 311 (21), 2167-68. PubMedID: 24839118
Paz-Filho, G, et al. (2011), ‘Associations between adipokines and obesity-related cancer.’, Front Biosci (Landmark Ed), 16 1634-50. PubMedID: 21196253
Tsai, F and WJ Coyle (2009), ‘The microbiome and obesity: is obesity linked to our gut flora?’, Curr Gastroenterol Rep, 11 (4), 307-13. PubMedID: 19615307