One of the most robust observations in the biology of aging is that caloric restriction (CR) extends life in a variety of species. Although CR results in a severalfold decrease in fat mass (FM), the role of fat on life extension was considered to be minimal. Two main reasons accounted for this belief. First, although increased FM is associated with changes in substrate oxidation and in glucose homeostasis, in part through the effects of free fatty acids (FFA) and glycerol, several studies have suggested that longevity is determined independent of FM. Second, CR has systemic effects on a range of functions including neurological, endocrine, reproductive, immunological and antineoplastic, none of which have been historically linked to fat. In the last few years, an explosion of evidence has demonstrated that fat tissue is a very active endocrine gland which secretes a variety of peptides (such as leptin and plasminogen activating inhibitor-1), cytokines (such as tumor necrosis factor), and complement factors (such as D, C3, and B). This is in addition to the presence of substrates, such as glycerol and FFA, which are stored and released by fat cells and are known to have a major role in hepatic and peripheral glucose metabolism. We propose that many of the systemic effects of CR can now be explained by the chronic effects related to decreased plasma levels of peptides, cytokines, complement factors, and substrates. In fact, all of the benefits of CR on the neuroendocrine system and those related to the improvement in glucose homeostasis can be attributed to decrease in adipose cells and their products. Other evidence from epidemiological data in human obesity supports the role of fat mass and its body distribution as a risk factor for morbidity and mortality in humans due to impaired glucose metabolism (similar to rodents), for cancer (similar to rodents), and for the development of atherosclerotic vascular disease (in humans). If all or most of the life-extending benefits of CR can be attributed to decreased fat stores, the expression of specific candidate proteins may be explored and manipulated in the search for the most powerful adipose-dependent signals that modulate life expectancy.

Revisiting the role of fat mass in the life extension induced by caloric restriction. commentary. author's reply

Obesity is a notable risk factor for developing type 2 diabetes, augmenting the concern of obese diabetes (ObD). Anti-obesity and antioxidant effects of red pepper seeds extract (RPSE) have increased our expectations that RPSE would also improve the pathological phenotypes of obese diabetes. Therefore, we hypothesized that RPSE would have an anti-diabetic effect in ObD mice. Animals were assigned either as follows: (1) db/+, (2) db/db control, (3) RPSE (200 mg/kg bw), or (4) a comparative control (metformin 150 mg/kg bw). RPSE was orally administered daily for 8 weeks. As a result, RPSE supplementation improved diabetic phenotypes, including fasting glucose, hemoglobin (HbA1c), and insulin levels. Pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6), and triglycerides were reduced in RPSE-treated mice. RPSE supplementation also diminished the rate-limiting enzymes of gluconeogenesis, including glucose 6-phosphatas (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK), in the liver. RPSE supplementation increased the phosphorylation of forkhead box protein O1 (FOXO1) and AMP-activated protein kinase (AMPK), which underlined the mechanism of the anti-diabetic effects of RPSE. Taken together, RPSE has the potential to improve glycemic control by repressing hepatic gluconeogenesis via the phosphorylation of FOXO1 and AMPK in ObD mice.

Red pepper (Capsicum annuum l.) seed extract improves glycemic control by inhibiting hepatic gluconeogenesis via phosphorylation of foxo1 and ampk in obese diabetic db/db mice

Obesity is occurring due to continue taken high fat diet; this is the fast-growing problem reaching epidemic proportion globally. Ursolic acid altered the abnormal glucose metabolism in diabetic rats. In this experimental protocol, we examine ursolic acid (UA) anti-obesity effect against streptozotocin (STZ) and high-fat diet-induced obesity in rats. Orally administered the ursolic acid (2.5, 5 and 10 mg/kg) dose to the hyperglycemic rats for 8 weeks and estimated the blood glucose level at different time intervals. Biochemical, hepatic, lipid, renal and antioxidant parameters were estimated. Traf-4, Mapk-8, Traf-6 and genes such as Ins-1, ngn-3 and Pdx-1 mRNA expression were estimated using qRT-PCR to scrutinize the molecular mechanism in MAPK downstream JNK cascade and insulin pathway signalling pathways. Ursolic acid significantly (p<0.001) down-regulated the blood glucose level at dose dependent manner. Its also reduced the plasma insulin level, non-essential fatty acid and increased the level of adiponectin as compared to obese control group rats. Ursolic acid treated group rats reduced the level of total cholesterol and triglycerides. Ursolic-acid-treated rats have been shown to decrease oxidative stress in pancreatic tissue by restoring the free radical effect of scavenging, suppress the Traf-6, Mapk-8 and Traf-4 mRNA expression, enhance the expression of Pdx-1, Ins-1 and Ngn-3 and ensure the regeneration of pancreas β cells and therefore pancreas insulin. The current result suggested the anti-obese effect of ursolic acid against high fat diet (HFD) induced obese rats via alteration of insulin and JNK signaling pathway.

/pdf/anti-obesity-and-anti-diabetic-effect-of-ursolic-acid-1edquuuj.pdf

Anti-obesity and Anti-diabetic Effect of Ursolic Acid against Streptozotocin/High Fat Induced Obese in Diabetic Rats.

Soybean koji refers to steamed soybeans inoculated with microbial species. Soybean fermentation improves the health benefits of soybeans. Obesity is a serious health concern owing to its increasing incidence rate and high association with other metabolic diseases. Therefore, we investigated the effects of soybean and soybean koji on high-fat diet-induced obesity in rats. Five-week-old male Sprague-Dawley rats were randomly divided into four groups (n = 8/group) as follows: (1) regular diet (RD), (2) high-fat diet (HFD), (3) HFD + steamed soybean (HFD+SS), and (4) HFD + soybean koji (HFD+SK). SK contained more free amino acids and unsaturated fatty acids than SS. In a rat model of obesity, SK consumption significantly alleviated the increase in weight of white adipose tissue and mRNA expression of lipogenic genes, whereas SS consumption did not. Both SS and SK reduced serum triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels, and increased high-density lipoprotein cholesterol levels. SS and SK also inhibited lipid accumulation in the liver and white adipose tissue and reduced adipocyte size. Although both SS and SK could alleviate HFD-induced dyslipidemia, SK has better anti-obesity effects than SS by regulating lipogenesis. Overall, SK is an excellent functional food that may prevent obesity.

https://www.mdpi.com/1660-4601/18/11/6032/pdf

Effect of Soybean and Soybean Koji on Obesity and Dyslipidemia in Rats Fed a High-Fat Diet: A Comparative Study.

Animal studies have shown that capsaicin plays a positive role in weight management. However, the results in human research are controversial. Therefore, the present systematic review and meta-analysis aimed to evaluate the effect of capsaicin on weight loss in adults. We searched PubMed, Embase, China Biomedical Literature Database (CBM), Cochrane library and clinical registration centre, identifying all randomised controlled trials (RCT) published in English and Chinese to 3 May 2022. A random-effect model was used to calculate the weighted mean difference (WMD) and 95 % CI. Heterogeneity between studies was assessed by the Cochran Q statistic and I-squared tests (I2 ). Statistical analyses were performed using STATA version 15.1. P-values < 0·05 were considered as statistically significant. From 2377 retrieved studies, fifteen studies were finally included in the meta-analyses. Fifteen RCT with 762 individuals were included in our meta-analysis. Compared with the control group, the supplementation of capsaicin resulted in significant reduction on BMI (WMD: -0·25 kg/m2, 95 % CI = -0·35, -0·15 kg/m2, P < 0·05), body weight (BW) (WMD: -0·51 kg, 95 % CI = -0·86, -0·15 kg, P < 0·05) and waist circumference (WC) (WMD: -1·12 cm, 95 % CI = -2·00, -0·24 cm, P < 0·05). We found no detrimental effect of capsaicin on waist-to-hip ratio (WMD: -0·05, 95 % CI = -0·17, 0·06, P > 0·05). The current meta-analysis suggests that capsaicin supplementation may have rather modest effects in reducing BMI, BW and WC for overweight or obese individuals. 

The effects of capsaicin intake on weight loss among overweight and obese subjects: A systematic review and meta-analysis of randomized controlled trials

Obesity is the main risk factor for metabolic syndromes and there has been an upsurge in demand for effective therapeutic strategies. This study investigated the effect of red pepper seed water extract (RPS) on the process of differentiation in 3T3-L1 adipocytes. RPS treatment significantly suppressed cellular lipid accumulation and reduced the expression of adipocytes-associated proteins, peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT/enhancer-binding proteins α (C/EBP α), sterol regulatory element binding protein-1c (SREBP-1c), as well as fatty acid synthase (FAS), and fatty acid binding protein 4 (FABP4). The inhibitory effect of RPS on differentiation was mainly through the modulation of the C/EBP β and C/EBP δ expression at the early phase of differentiation. Moreover, at the early phase of differentiation, RPS markedly increased the phosphorylation of AMP-activated protein kinase (AMPK). Such enhancing effect of RPS was abolished in the presence of compound C. Our results suggest that ...

Red Pepper Seed Inhibits Differentiation of 3T3-L1 Cells during the Early Phase of Adipogenesis via the Activation of AMPK

In this study, the protective effect of red pepper seed water extract (RPS) against the obesity in high fat diet (HFD)-fed mice was investigated (HFD control group, and HFD group treated with 100 or 200 mg/kg body weight of RPS for 13 weeks). The application of RPS partially reversed the HFD-induced increases in body weight and adipose tissue weight. The patterns of the adipose tissue weights were parallel to the patterns of fat area, as measured in DXA procedure. In the adipose tissue, RPS suppressed the expression of adipogenic transcription factors and adipose marker genes. AMP-activated protein kinase activation was observed in the adipose tissue by RPS treatment. In addition, RPS improved high homeostasis model assessment of insulin resistance and hyperlipidemia in HFD fed mice. These findings suggest that RPS can be used as a potential therapeutic substance for reducing body fat and obesity related diseases.

Red pepper seed water extract suppresses high-fat diet-induced obesity in C57BL/6 mice

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Red Pepper Seed Inhibits Differentiation of 3T3-L1 Cells during the Early Phase of Adipogenesis via the Activation of AMPK

Red pepper seed water extract suppresses high-fat diet-induced obesity in C57BL/6 mice