Preventive and Therapeutic Effects of Krill Oil on Obesity and Obesity-Induced Metabolic Syndromes in High-Fat Diet-Fed Mice

Abstract

Obesity increases the risks of metabolic syndromes including nonalcoholic fatty liver disease (NAFLD), diabetic dyslipidemia, and chronic kidney disease. Dietary krill oil (KO) has shown antioxidant and anti-inflammatory properties, thereby being a therapeutic potential for obesity-induced metabolic syndromes. Thus, the effects of KO on lipid metabolic alteration were examined in a high-fat diet (HFD)-fed mice model. The HFD model (n = 10 per group) received an oral gavage with distilled water as a control, metformin at 250 mg/kg, and KO at 400, 200, and 100 mg/kg for 12 weeks. The HFD-induced weight gain and fat deposition were significantly reduced in the KO treatments compared with the control. Blood levels were lower in parameters for NAFLD (e.g., alanine aminotransferase, and triglyceride), type 2 diabetes (e.g., glucose and insulin), and renal dysfunction (e.g., blood urea nitrogen and creatinine) by the KO treatments. The KO inhibited lipid synthesis through the modification of gene expressions in the liver and adipose tissues and adipokine-mediated pathways. Furthermore, KO showed hepatic antioxidant activities and glucose lowering effects. Histopathological analyses revealed that the KO ameliorated the hepatic steatosis, pancreatic endocrine/exocrine alteration, adipose tissue hypertrophy, and renal steatosis. These analyses suggest that KO may be promising for inhibiting obesity and metabolic syndromes.

Keywords: HFD; NAFLD; PUFA; T2D; diabetes; dyslipidemia; marine; metformin; obesity; steatosis.

Figure 1

Body weight changes and energy metabolism: (a) kinetic weight changes; (b) total weight gains for 12 weeks; (c) daily intakes of diet energy; (d) fecal lipid excretions. Values are expressed as the means ± standard deviations (SDs). ^‡ p < 0.01 and ^† p < 0.05 versus the NFD. ^*a, ^*b, ^*c, and ^*d: p < 0.05 versus the HFD control (HFD) in the MET, KO400, KO200, and KO100, respectively. ** p < 0.01 versus the HFD.

Figure 2

Body fat deposition: (a) Representative images of body fat deposition in necropsy and live dual-energy X-ray absorptiometry (DEXA). In the live DEXA images, red, yellow, and blue indicate high-, intermediate-, and low-density fats, respectively. Scale bars = 2 cm. (b,c) Fat densities in total body and the abdominal region. Values are expressed as the mean ± SD. ^‡ p < 0.01 versus the NFD. ** p < 0.01 versus the HFD.

Figure 3

Hepatic antioxidant and glucose-regulating enzyme activities. The levels of hepatic malondialdehyde (MDA) and glutathione (GSH) and the activities of catalase and superoxide dismutase (SOD) were assessed for antioxidant activities, and glucokinase (GK), glucose-6-phosphatase (G6pase), and phosphoenolpyruvate carboxykinase (PEPCK) were assessed for glucose-regulating enzyme activities. Values are expressed as the mean ± SD. ^‡ p < 0.01 and ^† p < 0.05 versus the NFD. ** p < 0.01 and * p < 0.05 versus the HFD.

Figure 4

Gene expressions involved in metabolic alteration. Gene expressions of acetyl-CoA carboxylase 1 (ACC1), AMP-activated protein kinase (AMPK)α1, and AMPKα2 were assessed in the liver, and the expressions of leptin, adiponectin, uncoupling protein (UCP)2, CCAAT-enhancer-binding protein (C/EBP)α, C/EBPβ, sterol-regulatory-element-binding protein 1c (SREBP1c), peroxisome proliferator-activated receptor (PPAR)α, PPARγ, and fatty acid synthase (FAS) were assessed in the periovarian fat tissues. Values are expressed as the mean ± SD. ^‡ p < 0.01 and ^† p < 0.05 versus the NFD. ** p < 0.01 and * p < 0.05 versus the HFD.

Figure 5

Histopathological changes in the liver: (a) Representative images in stains with hematoxylin and eosin and Oil red O. CV = central vein; PT = portal triad. Scale bars = 50 μm. (b,c) Sizes of the hepatocytes and Oil red O-stained areas. Values are expressed as the mean ± SD. ^‡ p < 0.01 and ^† p < 0.05 versus the NFD. ** p < 0.01 versus the HFD.

Figure 6

Histopathological changes in the pancreas: (a) Representative images in stains with hematoxylin and eosin (HE) and immunostains for insulin (IR) and glucagon (GR). In the HE stains, pancreatic islet (IS) and the exocrine duct (EX) of the acinar region (upper) were high-magnified in the middle and lower area, respectively. Scale bars = 50 μm. (b) The number and size of the islets and acinar region containing zymogen granules. (c) The number of IR and GR cells and the ratio of IR to GR cells. Values are expressed as the mean ± SD. ^‡ p < 0.01 versus the NFD; ** p < 0.01 versus the HFD.

Figure 7

Histopathological changes in the kidney and fat tissue: (a) Representative images of the kidney and abdominal (A.) and periovarian (O.) fat tissue in stains with hematoxylin and eosin. Each image was high-magnified in the lower areas. Scale bars = 50 μm. (b) Renal tubular area with vacuolation. (c,d) Thickness of the A. fat and O. fat tissues and the size of their adipocytes. Values are expressed as the mean ± SD. ^‡ p < 0.01 and ^† p < 0.05 versus the NFD. ** p < 0.01 versus the HFD.