Exendin-4, a glucagon-like peptide-1 receptor agonist, alleviates muscular dysfunction and wasting in a streptozotocin-induced diabetic mouse model compared to metformin.

Diabetic muscular atrophy is becoming a fast-growing problem worldwide, including sarcopenia, which is associated with substantial mortality and morbidity risk. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been marketed and suggested to exert protective effects on not only glycemic control but also diabetic complications in diabetic patients. In this study, we investigated the therapeutic use of GLP-1RAs exendin-4, compared to antidiabetic drug metformin, for the intervention of muscular dysfunction during diabetic conditions using a streptozotocin (STZ)-induced diabetic mouse model. The results showed that both exendin-4 and metformin could effectively alleviate hyperglycemia in diabetic mice, and also counteract diabetes-induced muscle weight loss, weaker grip, and changes in muscle fiber cross-sectional area distribution. Unexpectedly, exendin-4, but not metformin, enhanced the increased kidney weight and histological change in diabetic mice. Taken together, these findings suggest that both exendin-4 and metformin could effectively improve the diabetic hyperglycemia and muscular dysfunction; but exendin-4 may aggravate the nephropathy in STZ-induced diabetic mice.

Dehulled Adlay (Coix lachryma-jobi L.) ameliorates hepatic gluconeogenesis and steatosis in streptozotocin/high-fat diet-induced diabetic rats.

Adlay (Coix lachryma-jobi L.) is a traditional Chinese herbal medicine with various biological activities. We investigated the anti-diabetic effects of different parts of adlay seeds, including polished adlay (PA), adlay bran (AB) and dehulled adlay (DA) in a streptozotocin (STZ)/high fat diet (HFD) diabetic rat model (DM). DM rats supplemented with or without PA (43%), AB (3%), or DA (46%) diet for 8 weeks. The plasma glucose and insulin levels and the insulin resistance index (HOMA-IR) were increased in DM group; among the three adlay diets, DA has the best effects attenuating all of these alterations in DM rats. Both AB and DA alleviated diabetes-impaired glucose tolerance. The increased hepatic phosphoenolpyruvate carboxykinase protein expression in DM group was improved by all of the three adlay diets. The increased ratio of glucose-6-phosphatase to glucokinase in DM group was suppressed by DA supplementation, further suggesting DA diet is most effective among the three diets. Both AB and DA diets had beneficial effects against hepatic steatosis, with better effects observed in DA group. These results suggest that the DA diet, composed of both polished adlay and adlay bran, possesses the best potential to improve glucose homeostasis, at least in part, by alleviating hepatic glucose metabolism and steatosis.

Antidiabetic Properties of Chitosan and Its Derivatives.

Diabetes mellitus is a chronic metabolic disorder. In addition to taking medication, adjusting the composition of the diet is also considered one of the effective methods to control the levels of blood glucose. Chitosan and its derivatives are natural and versatile biomaterials with health benefits. Chitosan has the potential to alleviate diabetic hyperglycemia by reducing hepatic gluconeogenesis and increasing skeletal muscle glucose uptake and utility. Scientists also focus on the glucose-lowering effect of chitosan oligosaccharide (COS). COS supplementation has the potential to alleviate abnormal glucose metabolism in diabetic rats by inhibiting gluconeogenesis and lipid peroxidation in the liver. Both high and low molecular weight chitosan feeding reduced insulin resistance by inhibiting lipid accumulation in the liver and adipose tissue and ameliorating chronic inflammation in diabetic rats. COS can reduce insulin resistance but has less ability to reduce hepatic lipids in diabetic rats. A clinical trial showed that a 3-month administration of chitosan increased insulin sensitivity and decreased body weight and triglycerides in obese patients. Chitosan and COS are considered Generally Recognized as Safe; however, they are still considered to be of safety concerns. This review highlights recent advances of chitosan and its derivatives in the glucose-lowering/antidiabetic effects and the safety.

Green sweet potato leaves increase Nrf2-mediated antioxidant activity and facilitate benzo[a]pyrene metabolism in the liver by increasing phase II detoxifying enzyme activities in rats.

Sweet potato leaves (SPL) are a valuable source of phytonutrients with nutritional and various health-promoting benefits. This study evaluated the effects of green and purple SPL supplementation on hepatic xenobiotic-metabolizing enzymes (XME) and membrane transporters, and benzo[a]pyrene (B[a]P) metabolism and B[a]P accumulation in rats. The experiments were conducted in standard and B[a]P-treated rat models. The first experiment showed that rats fed a diet containing 5% (w/w) green or purple SPL for two weeks showed increased hepatic activity of cytochrome P-450 (CYP)1A1/1A2 and glutathione S-transferase. Green SPL supplementation also increased the CYP2C, CYP2D and CYP3A and multidrug resistance-associated protein 2 levels in the liver. Notably, green and purple SPL induced nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 protein expression and reduced oxidative stress in the liver. The second experiment was to evaluate the effects of green and purple SPL supplementation on B[a]P metabolism and B[a]P accumulation in rats. Rats were fed SPL diets (the same as experiment I) for two weeks. When rats were exposed to a single dose (25 mg per kg BW) of B[a]P, green SPL had no effect on B[a]P-induced elevation of CYP1A1 activity but induced GST activity in the intestinal mucosa and the liver. Green SPL also increased hepatic UDP-glucuronosyltransferase activity and reduced B[a]P levels in the plasma, liver, and intestinal mucosa. A lower plasma 8-hydroxy-2'-deoxyguanosine level was found after B[a]P treatment only in the green SPL group. This study suggests that, in the standard rat model, green and purple SPL may increase Nrf2-mediated antioxidant activity and facilitate the xenobiotic detoxification process by increasing hepatic XME and transporters. When exposed to B[a]P, however, only green SPL consumption may increase hepatic B[a]P metabolism and lower the B[a]P level in the liver by increasing phase II detoxifying enzyme activities.

Improvement of Glycemic Control by a Functional Food Mixture Containing Maltodextrin, White Kidney Bean Extract, Mulberry Leaf Extract, and Niacin-Bound Chromium Complex in Obese Diabetic db/db Mice.

Steady-fiber granule (SFG) is a mixture containing maltodextrin, white kidney bean extract, mulberry leaf extract, and niacin-bound chromium complex. These active ingredients have been shown to be associated with improving either hyperglycemia or hyperlipidemia. This study was undertaken to evaluate the potential of SFG in the regulation of blood glucose homeostasis under obese diabetic conditions. Accordingly, db/db mice (8 weeks old) were administered with SFG at doses of 1.025, 2.05, or 5.125 g/kg BW daily via oral gavage for 4 weeks. No body weight loss was observed after SFG supplementation at all three doses during the experimental period. Supplementation of SFG at 2.05 g/kg BW decreased fasting blood glucose, blood fructosamine, and HbA1c levels in db/db mice. Insulin sensitivity was also improved, as indicated by HOMA-IR assessment and oral glucose tolerance test, although the fasting insulin levels were no different in db/db mice with or without SFG supplementation. Meanwhile, the plasma levels of triglyceride were reduced by SFG at all three doses. These findings suggest that SFG improves glycemic control and insulin sensitivity in db/db mice and can be available as an option for functional foods to aid in management of type 2 diabetes mellitus in daily life.

Correction: Green sweet potato leaves increase Nrf2-mediated antioxidant activity and facilitate benzo[a]pyrene metabolism in the liver by increasing phase II detoxifying enzyme activities in rats.

Correction for 'Green sweet potato leaves increase Nrf2-mediated antioxidant activity and facilitate benzo[a]pyrene metabolism in the liver by increasing phase II detoxifying enzyme activities in rats' by Ray-Yu Yang et al., Food Funct., 2022, https://doi.org/10.1039/d2fo01049f.

Fish Oil Enriched n-3 Polyunsaturated Fatty Acids Improve Ketogenic Low-Carbohydrate/High-Fat Diet-Caused Dyslipidemia, Excessive Fat Accumulation, and Weight Control in Rats.

Low-carbohydrate and high-fat diets have been used for body weight (BW) control, but their adverse effects on lipid profiles have raised concern. Fish oil (FO), rich in omega-3 polyunsaturated fatty acids, has profound effects on lipid metabolism. We hypothesized that FO supplementation might improve the lipid metabolic disturbance elicited by low-carbohydrate and high-fat diets. Male SD rats were randomized into normal control diet (NC), high-fat diet (HF), and low-carbohydrate/high-fat diet (LC) groups in experiment 1, and NC, LC, LC + 5% FO (5CF), and LC + 10% FO diet (10CF) groups in experiment 2. The experimental duration was 11 weeks. In the LC group, a ketotic state was induced, and food intake was decreased; however, it did not result in BW loss compared to either the HF or NC groups. In the 5CF group, rats lost significant BW. Dyslipidemia, perirenal and epididymal fat accumulation, hepatic steatosis, and increases in triglyceride and plasma leptin levels were observed in the LC group but were attenuated by FO supplementation. These findings suggest that a ketogenic low-carbohydrate/high-fat diet with no favorable effect on body weight causes visceral and liver lipid accumulation. FO supplementation not only aids in body weight control but also improves lipid metabolism in low-carbohydrate/high-fat diet-fed rats.

Polysaccharide-Rich Red Algae (Gelidium amansii) Hot-Water Extracts Alleviate Abnormal Hepatic Lipid Metabolism without Suppression of Glucose Intolerance in a Streptozotocin/Nicotinamide-Induced Diabetic Rat Model.

This study was designed to investigate the effects of polysaccharide-rich red algae (Gelidium amansii) hot-water extracts (GHE) on lipid and glucose metabolism in rats with streptozotocin (STZ)/nicotinamide (NA)-induced diabetes. Rats were divided into three groups: NC-normal control group), DM-diabetic group, and DG-diabetic group supplemented with GHE (5%). The experimental diet and drinking water were available ad libitum for 10 weeks. After the 10-week feeding duration, the body weight, liver weight, total adipose tissue weight, and hepatic TBARS and cholesterol levels were significantly increased, and hepatic glycogen content and adipose lipolysis rate were significantly decreased in the DM group, which could be effectively reversed by supplementation of GHE. However, GHE supplementation could not improve the glucose intolerance in DM rats. It was interesting to note that GHE supplementation could decrease the liver glucose-6-phosphotase activity, which was increased in DM rats. Taken together, these results suggested that GHE feeding may ameliorate abnormal hepatic lipid metabolism, but not glucose intolerance, in diabetic rats induced by STZ/NA.

Influence of Dietary Chitosan Feeding Duration on Glucose and Lipid Metabolism in a Diabetic Rat Model.

This study was designed to investigate the influence of dietary chitosan feeding-duration on glucose and lipid metabolism in diabetic rats induced by streptozotocin and nicotinamide [a non-insulin-dependent diabetes mellitus (NIDDM) model]. Male Sprague-Dawley rats were used as experimental animals and divided into short-term (6 weeks) and long-term (11 weeks) feeding durations, and each duration contained five groups: (1) control, (2) control + 5% chitosan, (3) diabetes, (4) diabetes + 0.8 mg/kg rosiglitazone (a positive control), and (5) diabetes + 5% chitosan. Whether the chitosan feeding was for 6 or 11 weeks, the chitosan supplementation decreased blood glucose and lipids levels and liver lipid accumulation. However, chitosan supplementation decreased plasma tumor necrosis factor (TNF)-α, insulin levels, alanine aminotransferase (ALT) activity, insulin resistance (HOMA-IR), and adipose tissue lipoprotein lipase activity. Meanwhile, it increased plasma high-density lipoproteins (HDL)-cholesterol level, plasma angiopoietin-like-4 protein expression, and plasma triglyceride levels (at 11-week feeding duration only). Taken together, 11-week (long-term) chitosan feeding may help to ameliorate the glucose and lipid metabolism in a NIDDM diabetic rat model.

Chitosan Oligosaccharide Alleviates Abnormal Glucose Metabolism without Inhibition of Hepatic Lipid Accumulation in a High-Fat Diet/Streptozotocin-Induced Diabetic Rat Model.

This study investigated the effects of chitosan oligosaccharide (COS) on glucose metabolism and hepatic steatosis in a high-fat (HF) diet/streptozotocin-induced diabetic rat model. Male Wistar rats were divided into: (1) normal control (NC group), (2) HF diet (HF group), (3) streptozotocin (STZ)-induced diabetes with HF diet (DF group), and DF group supplemented with (4) 0.5% COS (D0.5F group), (5) 1% COS (D1F group), and (6) 5% COS (D5F group) for 4 weeks. COS supplementation significantly decreased the plasma glucose, BUN, creatinine, uric acid, triglyceride (TG), and total cholesterol (TC) levels, and hepatic glucose-6-phosphatase activity, and significantly increased hepatic hexokinase activity and glycogen content in diabetic rats; but the increased hepatic TG and TC levels could not be significantly decreased by COS supplementation. Supplementation of COS increased superoxide dismutase activity and decreased lipid peroxidation products in the diabetic rat livers. COS supplementation significantly increased phosphorylated AMP-activated protein kinase (AMPK) protein expression, and attenuated protein expression of hepatic phosphoenolpyruvate carboxykinase (PEPCK) and phosphorylated p38 and renal sodium-glucose cotransporter-2 (SGLT2) in diabetic rats. These results suggest that COS may possess a potential for alleviating abnormal glucose metabolism in diabetic rats through the inhibition of hepatic gluconeogenesis and lipid peroxidation and renal SGLT2 expression.

Effects and Mechanisms of Chitosan and ChitosanOligosaccharide on Hepatic Lipogenesis and Lipid Peroxidation, Adipose Lipolysis, and Intestinal Lipid Absorption in Rats with High-Fat Diet-Induced Obesity.

Chitosan and its derivative, chitosan oligosaccharide (CO), possess hypolipidemic and anti-obesity effects. However, it is still unclear if the mechanisms are different or similar between chitosan and CO. This study was designed to investigate and compare the effects of CO and high-molecular-weight chitosan (HC) on liver lipogenesis and lipid peroxidation, adipose lipolysis, and intestinal lipid absorption in high-fat (HF) diet-fed rats for 12 weeks. Rats were divided into four groups: normal control diet (NC), HF diet, HF diet+5% HC, and HF diet+5% CO. Both HC and CO supplementation could reduce liver lipid biosynthesis, but HC had a better effect than CO on improving liver lipid accumulation in HF diet-fed rats. The increased levels of triglyceride decreased lipolysis rate, and increased lipoprotein lipase activity in the perirenal adipose tissue of HF diet-fed rats could be significantly reversed by both HC and CO supplementation. HC, but not CO, supplementation promoted liver antioxidant enzymes glutathione peroxidase and superoxide dismutase activities and reduced liver lipid peroxidation. In the intestines, CO, but not HC, supplementation reduced lipid absorption by reducing the expression of fabp2 and fatp4 mRNA. These results suggest that HC and CO have different mechanisms for improving lipid metabolism in HF diet-fed rats.

Polysaccharide-rich red algae (Gelidium amansii) hot-water extracts ameliorate the altered plasma cholesterol and hepatic lipid homeostasis in high-fat diet-fed rats.

We have demonstrated that red algae Gelidium amansii (GA) hot-water extract (GHE) is a polysaccharide-rich fraction, containing 68.54% water-soluble indigestible carbohydrate polymers; the molecular weight of major polysaccharide is 892. Here, we investigated the mechanisms of GHE on plasma and hepatic lipid metabolisms in high-fat (HF) diet-fed rats. Rats were divided into: normal diet group, HF-diet group, HF-diet+5% GHE group, and HF-diet+1% cholestyramine group. GHE supplementation for 8 weeks significantly decreased plasma cholesterol, LDL-C, and VLDL-C levels and increased the fecal triglyceride and bile acid excretion in HF diet-fed rats. GHE group has lower lipid contents in the liver and adipose tissues. GHE supplementation decreased the activities of acetyl-CoA carboxylase, fatty acid synthase, and HMG-CoA reductase in the livers. The levels of increased phosphorylated AMP-activated protein kinase (AMPK), peroxisome proliferator activated receptor (PPAR)-α, farnesoid-X receptor (FXR), low density lipoprotein receptor (LDLR), and cytochrome P450-7A1 (CYP7A1) protein expression, and the decreased PPAR-γ protein expression in the livers were observed in GHE group. These results suggest that GHE supplementation is capable of interfering in cholesterol metabolism and increasing hepatic LDLR and CYP7A1 expression to decrease blood cholesterol, and activating FXR and AMPK to inhibit lipogenic enzyme activities and reduce the hepatic lipid accumulation.

Effects of Chitosan Oligosaccharide on Plasma and Hepatic Lipid Metabolism and Liver Histomorphology in Normal Sprague-Dawley Rats.

Chitosan oligosaccharide is known to ameliorate hypercholesterolemia and diabetes. However, some studies found that chitosan oligosaccharide might induce mild to moderate hepatic damage in high-fat (HF) diet-induced obese rats or diabetic rats. Chitosan oligosaccharide can be as a dietary supplement, functional food, or drug. Its possible toxic effects to normal subjects need to be clarified. This study is designed to investigate the effects of chitosan oligosaccharide on plasma and hepatic lipid metabolism and liver histomorphology in normal Sprague-Dawley rats. Diets supplemented with 5% chitosan oligosaccharide have been found to induce liver damage in HF diet-fed rats. We therefore selected 5% chitosan oligosaccharide as an experimental object. Rats were divided into: a normal control diet group and a normal control diet +5% chitosan oligosaccharide group. The experimental period was 12 weeks. The results showed that supplementation of 5% chitosan oligosaccharide did not significantly change the body weight, food intake, liver/adipose tissue weights, plasma lipids, hepatic lipids, plasma levels of AST, ALT, and TNF-α/IL-6, hepatic lipid peroxidation and anti-oxidative enzyme activities, fecal lipids, and liver histomorphology in normal rats. These findings suggest that supplementation of 5% chitosan oligosaccharide for 12 weeks may not induce lipid metabolism disorder and liver toxicity in normal rats.

Comparative Effects and Mechanisms of Chitosan and Its Derivatives on Hypercholesterolemia in High-Fat Diet-Fed Rats.

The present study investigated and compared the effects of different molecular weights of chitosan (high molecular weight chitosan (HC) and low molecular weight chitosan (LC)) and its derivatives (chitosan oligosaccharide (CO)) on cholesterol regulation in high-fat (HF) diet-fed rats. A diet supplementation of 5% HC, 5% LC, or 5% CO for 8 weeks showed hypocholesterolemic potential in HF diet-fed rats. Unexpectedly, a 5% CO-supplemented diet exerted hepatic damage, producing increased levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and tumor necrosis factor-alpha (TNF-α). The supplementation of HC and LC, unlike CO, significantly decreased the hepatic total cholesterol (TC) levels and increased the fecal TC levels in HF diet-fed rats. The hepatic protein expression of the peroxisome proliferator-activated receptor-α (PPARα) in the HF diet-fed rats was markedly decreased, which could be significantly reversed by both HC and LC, but not CO, supplementation. Unlike the supplementation of CO, both HC and LC supplementation could effectively reverse the HF-inhibited/induced gene expressions of the low-density lipoprotein receptor (LDLR) and cholesterol 7α-hydroxylase (CYP7A1), respectively. The upregulated intestinal acyl-CoA cholesterol acyltransferase 2 (ACAT2) protein expression in HF diet-fed rats could be reversed by HC and LC, but not CO, supplementation. Taken together, a supplementation of 5% CO in HF diet-fed rats may exert liver damage via a higher hepatic cholesterol accumulation and a higher intestinal cholesterol uptake. Both HC and LC effectively ameliorated the hypercholesterolemia and regulated cholesterol homeostasis via the activation and inhibition of hepatic (AMPKα and PPARα) and intestinal (ACAT2) cholesterol-modulators, respectively, as well as the modulation of downstream signals (LDLR and CYP7A1).

The Anti-Obesity Effect of Polysaccharide-Rich Red Algae (Gelidium amansii) Hot-Water Extracts in High-Fat Diet-Induced Obese Hamsters.

This study investigated the anti-obesity effect of a polysaccharide-rich red algae Gelidium amansii hot-water extract (GHE) in high-fat (HF) diet-induced obese hamsters. GHE contained 68.54% water-soluble indigestible carbohydrate polymers. Hamsters were fed with a HF diet for 5 weeks to induce obesity, and then randomly divided into: HF group, HF with 3% guar gum diet group, HF with 3% GHE diet group, and HF with orlistat (200 mg/kg diet) group for 9 weeks. The increased weights of body, liver, and adipose in the HF group were significantly reversed by GHE supplementation. Lower plasma leptin, tumor necrosis factor-α, and interleukin-6 levels were observed in the GHE+HF group compared to the HF group. GHE also increased the lipolysis rate and decreased the lipoprotein lipase activity in adipose tissues. GHE induced an increase in the phosphorylation of AMP-activated protein kinase (AMPK) and the protein expressions of peroxisome proliferator-activated receptor alpha (PPARα) and uncoupling protein (UCP)-2 in the livers. The decreased triglyceride and total cholesterol in the plasma and liver were also observed in obese hamsters fed a diet with GHE. These results suggest that GHE exerts a down-regulation effect on hepatic lipid metabolism through AMPK phosphorylation and up-regulation of PPARα and UCP-2 in HF-induced obese hamsters.

Omega-3 Fatty Acids-Enriched Fish Oil Activates AMPK/PGC-1α Signaling and Prevents Obesity-Related Skeletal Muscle Wasting.

Obesity is known to cause skeletal muscle wasting. This study investigated the effect and the possible mechanism of fish oil on skeletal muscle wasting in an obese rat model. High-fat (HF) diets were applied to induce the defects of lipid metabolism in male Sprague-Dawley rats with or without substitution of omega-3 fatty acids-enriched fish oil (FO, 5%) for eight weeks. Diets supplemented with 5% FO showed a significant decrease in the final body weight compared to HF diet-fed rats. The decreased soleus muscle weights in HF diet-fed rats could be improved by FO substitution. The decreased myosin heavy chain (a muscle thick filament protein) and increased FOXO3A and Atrogin-1 (muscle atrophy-related proteins) protein expressions in soleus muscles of HF diet-fed rats could also be reversed by FO substitution. FO substitution could also significantly activate adenosine monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation, peroxisome-proliferator-activated receptor-γ (PPARγ) coactivator 1α (PGC-1α), and PPARγ protein expression and lipoprotein lipase (LPL) mRNA expression in soleus muscles of HF diet-fed rats. These results suggest that substitution of FO exerts a beneficial improvement in the imbalance of lipid and muscle metabolisms in obesity. AMPK/PGC-1α signaling may play an important role in FO-prevented obesity-induced muscle wasting.

Resistant Maltodextrin Ameliorates Altered Hepatic Lipid Homeostasis via Activation of AMP-Activated Protein Kinase in a High-Fat Diet-Fed Rat Model.

Many studies have shown that resistant maltodextrin (RMD) possesses blood cholesterol lowering and anti-obesity effects. In order to investigate the effect of RMD on lipid metabolism in the liver, rats were fed with a high-fat (HF) diet for 7 weeks to induce hyperlipidemia and fatty liver. Normal control rats were fed with a normal diet. HF-diet-fed rats were treated with 5% RMD for 8 weeks. The results showed that the increased plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, the increased hepatic triglyceride and total cholesterol levels, and fatty liver in HF-diet-fed rats were significantly decreased after supplementation with RMD. Supplementation with RMD significantly (1) induced AMP-activated protein kinase (AMPK) phosphorylation; (2) inhibited the activities of acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and HMG-CoA reductase (HMGCR); (3) suppressed the protein expression of peroxisome proliferator activated receptor (PPAR)-γ; (4) increased ß-oxidation of fatty acids by increasing the protein expression carnitine palmitoyl transferase 1α (CPT-1α) in the livers of HF-diet-fed rats. Taken together, supplementation of RMD was capable of inhibiting lipogenic enzyme activities and inducing fatty acid ß-oxidation through increasing AMPK activation, thereby reducing lipid accumulation in the liver.

Functional Comparison of High and Low Molecular Weight Chitosan on Lipid Metabolism and Signals in High-Fat Diet-Fed Rats.

The present study examined and compared the effects of low- and high-molecular weight (MW) chitosan, a nutraceutical, on lipid metabolism in the intestine and liver of high-fat (HF) diet-fed rats. High-MW chitosan as well as low-MW chitosan decreased liver weight, elongated the small intestine, improved the dysregulation of blood lipids and liver fat accumulation, and increased fecal lipid excretion in rats fed with HF diets. Supplementation of both high- and low-MW chitosan markedly inhibited the suppressed phosphorylated adenosine monophosphate (AMP)-activated protein kinase-α (AMPKα) and peroxisome proliferator-activated receptor-α (PPARα) protein expressions, and the increased lipogenesis/cholesterogenesis-associated protein expressions [peroxisome proliferator-activated receptor-γ (PPARγ), sterol regulatory element binding protein-1c and -2 (SREBP1c and SREBP2)] and the suppressed apolipoprotein E (ApoE) and microsomal triglyceride transfer protein (MTTP) protein expressions in the livers of rats fed with HF diets. Supplementation with both a low- and high-MW chitosan could also suppress the increased MTTP protein expression and the decreased angiopoietin-like protein-4 (Angptl4) expression in the intestines of rats fed with HF diets. In comparison between low- and high-MW chitosan, high-MW chitosan exhibits a higher efficiency than low-MW chitosan on the inhibition of intestinal lipid absorption and an increase of hepatic fatty acid oxidation, which can improve liver lipid biosynthesis and accumulation.

Fish Oil Supplementation Alleviates the Altered Lipid Homeostasis in Blood, Liver, and Adipose Tissues in High-Fat Diet-Fed Rats.

This study investigated the effects of dietary supplementation of fish oil on the signals of lipid metabolism involved in hepatic cholesterol and triglyceride influx and excretion in high-fat diet (HFD)-fed rats. Fish oil (FO) repressed body (HFD, 533 ± 18.2 g; HFD+FO, 488 ± 28.0 g, p < 0.05) and liver weights (HFD, 5.7 ± 0.6 g/100 g of body weight; HFD+FO, 4.8 ± 0.4 g/100 g of body weight, p < 0.05) in HFD-fed rats. Fish oil could also improve HFD-induced imbalance of lipid metabolism in blood, liver, and adipose tissues including the significant decreases in plasma and liver total cholesterol (TC) (plasma-HFD, 113 ± 33.6 mg/dL; HFD+FO, 50.0 ± 5.95 mg/dL, p < 0.05; liver-HFD, 102 ± 13.0 mg/g liver; [corrected] HFD+FO, 86.6 ± 7.81 mg/g liver, [corrected] p < 0.05), blood, liver, and adipose triglyceride (TG) (blood-HFD, 52.5 ± 20.4 mg/dL; HFD+FO, 29.8 ± 4.30 mg/dL, p < 0.05; liver-HFD, 56.2 ± 10.0 mg/g liver; [corrected] HFD+FO, 30.3 ± 5.28 mg/g liver, [corrected] p < 0.05; adipose-HFD, 614 ± 73.2 mg/g liver, [corrected] HFD+FO, 409 ± 334 mg/g of adipose tissue, [corrected] p < 0.05), and low density (HFD, 79.8 ± 40.9 mg/dL; HFD+FO, 16.6 ± 5.47 mg/dL, p < 0.05) and very-low-density (HFD, 49.7 ± 33.3 mg/dL; HFD+FO, 10.4 ± 3.45 mg/dL, p < 0.05) lipoprotein and the significant increases in fecal TC (HFD, 12.2 ± 0.67 mg/g feces; [corrected] HFD+FO, 16.3 ± 2.04 mg/g feces, [corrected] < 0.05) and TG (HFD, 2.09 ± 0.10 mg/g feces; [corrected] HFD+FO, 2.38 ± 0.22 mg/g feces, [corrected] p < 0.05) and lipoprotein lipase activity of adipose tissues (HFD, 16.6 ± 3.64 µM p-nitrophenol; HFD+FO, 24.5 ± 4.19 µM p-nitrophenol, p < 0.05). Moreover, fish oil significantly activated the protein expressions of hepatic lipid metabolism regulators (AMPKα and PPARα) and significantly regulated the lipid-transport-related signaling molecules (ApoE, MTTP, ApoB, Angptl4, ApoCIII, ACOX1, and SREBPF1) in blood or liver of HFD-fed rats. These results suggest that fish oil supplementation improves HFD-induced imbalance of lipid homeostasis in blood, liver, and adipose tissues in rats.