The Effects of Physical Activity on Hepatic Lipid Metabolism During Weight-Loss

Non-alcoholic fatty liver disease (NAFLD) develops as a result of physical inactivity and overnutrition. Changing dietary behaviors and increasing physical activity are common strategies used for weight-loss; however, it remains unclear what additional benefits are provided by incorporating physical activity in a weight-loss program for the treatment of NAFLD. The purpose of this study was to determine how physical activity reduces hepatic steatosis and changes the expression of hepatic lipogenic genes during weight-loss. Male C57BL/6 mice were fed either a low-fat (LFD; 10% kcal fat) or high-fat (HFD; 60% kcal fat) diet for 10-weeks. Following 10-weeks, the HFD group was randomly assigned to either a LFD (Diet) or LFD with physical activity (Diet+PA) to induce weight-loss for 8-weeks. After 8-weeks of weight-loss, reductions in body and liver mass were observed in both Diet and Diet+PA groups (see Table 1.). Interestingly, the Diet+PA group lost significantly (P\u3c0.05) more body mass than the Diet group. Reductions in body mass and HOMA-IR in the Diet and Diet+PA groups were matched by reductions in hepatic triglyceride levels. In the Diet+PA group, liver triglyceride and cholesterol levels were significantly (P\u3c0.05) lower than all other groups. The greater reduction in hepatic triglyceride levels from physical activity was due to significant (P\u3c0.05) reductions in the expression of lipogenic FASN and SCD-1 mRNA. Interestingly, physical activity did not alter fatty acid uptake or fatty acid oxidation as observed with CD36 and CPT-1a mRNA levels, respectively. Based on these findings, the addition of physical activity to a diet-induced weight-loss intervention provides a more effective approach for the treatment of NAFLD than dieting alone. Table 1. Whole body and hepatic metabolic characteristics following weight-loss. Variables LFD (n=12) HFD (n=12) Diet (n=12) Diet+PA (n=12) Body mass (g) 30.2 ± 1.1 48.8 ± 0.5* 30.3 ± 0.7† 26.1 ± 0.3*,†,‡ Liver mass (g) 1.2 ± 0.1 2.9 ± 0.2* 1.2 ± 0.1† 1.2 ± 0.1† Triglyceride (mg/dL) 99.4 ± 8.7 96.7 ± 5.5 88.3 ± 6.1 88.4 ± 4.8 Cholesterol (mg/dL) 153.5 ± 10.1 246.0 ± 8.7* 148.2 ± 15.5† 127.6 ± 4.7*,† HOMA-IR 22.9 ± 1.2 187.3 ± 7.5* 19.4 ± 8.8† 25.3 ± 10.5† Liver Tg (mg/mg tissue) 1.18 ± 0.14 2.53 ± 0.05* 0.96 ± 0.15† 0.58 ± 0.07*,†,‡ Liver Chol (μg/mg tissue) 437.0 ± 43.0 585.2 ± 54.4* 527.0 ± 56.5 324.0 ± 27.3*,†,‡ FASN mRNA 1.00 ± 0.20 1.90 ± 0.34* 2.10 ± 0.54* 0.46 ± 0.11*,†,‡ CD36/FAT mRNA 1.00 ± 0.22 0.19 ± 0.20* 0.97 ± 0.10† 0.80 ± 0.04† SCD-1 mRNA 1.00 ± 0.28 1.94 ± 0.83* 0.76 ± 0.13† 0.44 ± 0.05*,†,‡ CPT-1a mRNA 1.00 ± 0.18 0.74 ± 0.04* 0.62 ± 0.08* 0.73 ± 0.05* Note. Data are presented as mean ± SEM.*Significantly (P\u3c0.05) different than LFD; †significantly (P\u3c0.05) different than HFD; ‡significantly (P\u3c0.05) different than Diet

Independent and Combined Effects of Menhaden Oil and High Fructose on Hepatic Lipid Metabolism

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Influence of Menopausal Status on Lipids and Lipoproteins and Fat Mass Distribution: The Pioneer Project

Following menopause, fat redistribution and increased risk for dyslipidemia are common. The influence of menopause; however, on the associations between total and regional fat mass with lipids and lipoproteins remains unclear. PURPOSE: The purpose of this investigation was to determine the influence of menopausal status on associations between total and regional fat mass and lipids and lipoproteins. METHODS: Sedentary, non-smoking women (n=209) were grouped based on current menstrual status: premenopausal (n=143, mean±SD; age=42.7±7.7 yr, BMI=24.5±4.0 kg•m -2, WC=77.4±9.9 cm) or postmenopausal (n=66, mean±SD; age=52.9±5.3 yr, BMI= 24.9±4.2 kg•m -2, WC=78.8±9.9 cm). Fasting (12 hr) serum samples were analyzed for total cholesterol (TC), triglyceride (Tg), LDL-C, HDL-C, HDL2-C, and HDL3-C concentrations. Total (TF), abdominal (AF), hip (HF) and mid-thigh (MTF) fat mass were quantified by DXA. A MANCOVA was used to determine differences between groups for total and regional fat mass and lipids and lipoproteins controlling for HRT status. Stepwise multiple regression analysis was used to determine if menopausal status influenced the association of total and regional fat mass with lipids and lipoproteins. The criterion reference for statistical significance was set at a P \u3c 0.05. RESULTS: Postmenopausal women had significantly greater TC, HDL-C, LDL-C and HDL3-C concentrations than premenopausal women. No significant differences were observed between groups for total and regional fat mass. In premenopausal women, AF predicted TC, but no associations were observed in postmenopausal women. In premenopausal women, AF+HF and AF+TF were significant predictors of Tg and LDL-C, respectively. In contrast, only AF predicted Tg and LDL-C in postmenopausal women. AF+MTF best predicted HDL-C in premenopausal women; however, TF+MTF best predicted HDL-C in postmenopausal women. In premenopausal women, no associations were observed with HDL2-C or HDL3-C. TF and TF+MTF were best predictors of HDL2-C and HDL3-C, respectively in postmenopausal women. CONCLUSION: Menopausal status has an effect on lipid and lipoprotein-cholesterol concentrations, but not on total and regional fat mass. In addition, menopausal status had an influence on the associations of total and regional fat mass with lipids and lipoproteins

The Effects of Physical Activity on Markers of Hepatic Inflammation During Weight-Loss

Non-alcoholic fatty liver disease (NAFLD) represents a continuum that begins with accumulation of lipid in hepatic cells progressing to hepatic steatosis with inflammation (steatohepatitis), fibrosis, and cirrhosis. Weight-loss using dietary modification and physical activity are common strategies used for the treatment of NAFLD; however, it remains to be determined the effects of physical activity on hepatic inflammation during weight-loss. The purpose of this study was to determine the therapeutic role of physical activity on plasma and hepatic inflammatory markers during weight-loss. Male C57BL/6 mice were fed either a low-fat (LFD; 10% kcal fat) or high-fat (HFD; 60% kcal fat) diet for 10-weeks. Following 10-weeks, the HFD group was randomly assigned to either a LFD (Diet) or LFD with physical activity (Diet+PA) to induce weight loss for 8-weeks. After 8-weeks, reductions in body mass were observed in both Diet and Diet+PA groups (see Table 1.). Interestingly, the Diet+PA group lost significantly (P\u3c0.05) more body mass than the Diet group. Despite significant (P\u3c0.05) reductions in body mass and HOMA-IR, plasma TNF-α remained elevated in the Diet and Diet+PA groups. Moreover, Diet+PA plasma TNF-α was significantly (P\u3c0.05) greater than the HFD obese controls. Elevated plasma TNF-α in the Diet+PA was matched by a greater hepatic expression of IL-1β and IL-6 mRNA when compared to all groups. Interestingly, the expression of TGF-β1 mRNA was significantly (P\u3c0.05) reduced in the Diet+PA when compared to all groups. The elevated plasma TNF-α and expression of IL-1β and IL-6 mRNA are likely due to physical activity. It remains unclear as to the pro-inflammatory effects of physical activity during weight-loss; however, this may be part of a protective adaption to regular exercise. Furthermore, the reduced hepatic TGF-β1 mRNA levels suggest a protective strategy against fibrogenesis in the spectrum of liver disease. Table 1. Whole body and hepatic metabolic characteristics following weight-loss. Variables LFD (n=12) HFD (n=12) Diet (n=12) Diet+PA (n=12) Body mass (g) 30.2 ± 1.1 48.8 ± 0.5* 30.3 ± 0.7† 26.1 ± 0.3*,†,‡ HOMA-IR 22.9 ± 1.2 187.3 ± 7.5* 19.4 ± 8.8† 25.3 ± 10.5† IL-6 (pg/mL) 6.4 ± 0.7 6.2 ± 1.0 5.9 ± 0.9 6.4 ± 0.9 TNF-α (pg/mL) 30.8 ± 6.7 60.6 ± 5.3* 74.0 ± 8.1* 82.5 ± 7.7*,† IL-1β mRNA 1.00 ± 0.51 0.97 ± 0.34 1.20 ± 0.59 2.83 ± 0.62*,†,‡ IL-6 mRNA 1.00 ± 0.45 1.53 ± 0.50 1.16 ± 0.72 2.36 ± 0.55*,†,‡ TNF-α mRNA 1.00 ± 0.09 0.89 ± 0.08 0.94 ± 0.14 0.83 ± 0.06 TGF-β1 mRNA 1.00 ± 0.06 1.02 ± 0.06 1.02 ± 0.10 0.84 ± 0.05† Note. Data are presented as mean ± SEM. *Significantly (P\u3c0.05) different than LFD; †significantly (P\u3c0.05) different than HFD; ‡significantly (P\u3c0.05) different than Diet

The Lipogenic Effect of High-Fructose Consumption on NAFLD During Weight Loss

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The Effects of Physical Activity on Markers of Hepatic Lipid Metabolism during Weight Cycling

Non-alcoholic fatty liver disease (NAFLD) has emerged as the leading cause of liver disease and develops when the rate of hepatic triglyceride formation exceeds the rate of disposal. Weight loss is often prescribed to treat NAFLD; however, only one in six obese or overweight individuals who lose weight through diet are successful at maintaining weight loss resulting in weight regain (i.e., weight cycling). Purpose: To determine the effect of physical activity on the prevention of hepatic steatosis and expression of lipogenic genes during weight cycling. Methods: To induce obesity, male C57BL/6 mice were fed a 60% fat diet for 10-weeks. Following weight gain, mice were randomly assigned to a 10% fat diet either with (Diet+PA) or without (Diet) physical activity to induce weight loss for 8 weeks. Physical activity consisted of unrestricted access to running wheels. Following weight loss, the Diet and Diet+PA groups were switched back to a 60% fat diet for 10 weeks to cause weight regain. The Diet+PA had continued access to physical activity during weight regain. Age-matched lean and obese control mice were fed either a 10% fat diet (LF) or 60% fat diet (HF) for the entire 28 weeks of the study. Significant differences (P\u3c0.05) between groups were identified by one-way ANOVA. Results: Following weight regain, body mass of the Diet+PA was significantly lower than the HF (47.8 vs. 55.3 g) and Diet (47.8 vs. 53.9 g). No significant difference in body mass was observed between Diet and HF groups. The Diet+PA had significantly lower plasma cholesterol levels compared to HF (230.5 vs. 254.5 mg/dL) and Diet (230.5 vs. 271.9 mg/dL). In addition, the Diet+PA group had significantly lower total hepatic lipid (23.2 vs. 26.5%) when compared with Diet, which was associated with 60%, 50%, and 40% lower expression of lipogenic genes Fasn, Srebp1c, and Chrebp, respectively. No difference was noted between Diet and Diet+PA for the expression of lipogenic genes Scd1 and Acc1. Conclusions: These data suggests that the continued physical activity during weight cycling resulted in lower weight regain and reduced the accumulation of hepatic lipid by decreased de novo lipogenesis. Overall, the reduced expression of lipogenic related genes might point to a potential protective mechanism that physical activity has on the development of NAFLD during weight cycling

The Effects of Physical Activity on Markers of Adipose Inflammation during Weight Cycling

Weight loss using diet and exercise are the main treatment strategies for obesity; however, weight loss is rarely maintained resulting in weight regain or weight cycling. Obesity is associated with chronic low-grade inflammation resulting in the release of adipokines and activation of macrophages (M1) accelerating the development of insulin resistance. In contrast, the M2 macrophage phenotype is characterized by blocking inflammatory responses and promoting tissue repair. Despite the effectiveness of exercise on preventing comorbidities of obesity during weight-loss, the influence of physical activity during weight cycling on markers of adipose inflammation remains unclear. Purpose: The purpose of this study was to determine the role of physical activity on the expression of inflammatory markers in adipose tissue during weight cycling. Methods: Male C57BL/6 mice were randomly assigned to one of three groups for 28 weeks: a high-fat diet obese control (HFD; 60% kcal from fat), an alternating high-low-high fat diet group (Diet; 60%/10%/60% kcal from fat) to simulate weight cycling, or a diet-matched weight cycling group that had unrestricted access to running wheels (Diet+PA). After weight regain, MCP-1, CD11c, CD163, F4/80, TLR4, and TNFα mRNA levels were quantified in perigonadal adipose tissue using qRT-PCR. A one-way ANOVA was used to identify significant differences between groups with significance set at PWeight cycling without physical activity resulted in obesity and insulin resistance when compared to HFD obese controls. Interestingly, compared to the HFD control group, the Diet group demonstrated significantly greater expression of F4/80 (+50%), CD11c (+113%), TLR4 (+77%), and TNFα (+72%) mRNA, which may represent greater macrophage infiltration and M1 macrophage polarization. Physical activity during weight cycling resulted in lower weight regain compared to both HFD and Diet groups; however, mice still developed insulin resistance and increased expression of TLR4 (+76%), TNFα (+94%), and CD11c (+58%) suggesting increased M1 macrophage activation when compared to the HFD group. Conclusions: The data presented suggests weight cycling may accelerate the development of adipose dysfunction, and unrestricted physical activity appears to have minimal effects on the negative inflammatory effects of weight cycling

The Effect of a Western Diet on Hepatic Autophagy in Age Accelerated SAMP8 Mice

Non-alcoholic steatohepatitis (NASH) is characterized as a dysregulation of hepatic lipid metabolism and a chronic inflammatory state. It is hypothesized the link between lipid dysregulation and inflammation may be due in part to defective hepatic autophagy and reduced mitochondrial capacity to oxidize fatty acids. It remains to be determined; however, the effects of a Western diet on hepatic autophagy and mitochondrial function during aging. PURPOSE: The purpose of this study was to determine the effect of a high-fat high fructose diet (HFF) on markers of hepatic autophagy and mitochondrial function in an age accelerated mouse model. METHODS: Twenty week old, male and female, SAMP8 mice (n=49) were randomly assigned, matching for gender, to either a standard chow (SC) or HFF (45% fat, 24% fructose) diet for 32 weeks. Liver tissue was analyzed for mRNA expression of autophagic (BNIP3, Beclin 1, p62, and Atg7) and mitochondrial (PGC1α and COXIV) genes. Differences between gender and dietary groups were identified by a 2 x 2 ANOVA and statistical significance was set at p\u3c0.05. RESULTS: Following 32 weeks of feeding, male mice fed the HFF diet were significantly heavier than male mice in the SC group (31.6 g vs 26.5 g; p=0.001); however, no difference was observed between diet groups for female mice. The HFF diet resulted in higher autophagic activity as observed by Beclin 1 (+36%; p=0.001) and BNIP3 (+40%; P=0.003) expression. Despite the higher autophagic activity, p62 was higher (+31%; p\u3c0.001) in the HFF compared to the SC group, suggesting impaired autophagic flux. In addition, mitochondrial COXIV expression was elevated (+43%; P\u3c0.001) in the HFF group compared to the SC group suggesting increased β-oxidation. Overall, the expression of all autophagic and mitochondrial markers was higher in male compared to female mice; however, both sexes responded similarly to the HFF diet. CONCLUSION: Despite the higher expression of autophagic and mitochondrial genes, elevated expression of p62 suggests an impaired autophagic flux in age accelerated mice following a Western diet

Responses Of Lipids And Lipoproteins Following Acute And Training Resistance Exercise In Obese Postmenopausal Women

A single aerobic session and aerobic training can favorably modify lipids and lipoproteins in postmenopausal women, but the effects of a single resistance exercise session (RE) and resistance training (RT) remain equivocal. PURPOSE: To determine the acute effects of RE and chronic effects of 12 weeks of RT on lipid and lipoprotein-cholesterol concentrations in obese, postmenopausal women. METHODS: Sedentary, obese, non-smoking, postmenopausal women, not taking HRT, were divided into either an exercise group (E, n = 10; age = 65.7 ± 1.8 y; BMI = 32.6 ± 3.5 kg/m2) or control group (C, n = 11; age = 66.1 ± 3.0 y; BMI = 32.9 ± 4.3 kg/m2). Fasting (12 hr) blood samples were collected prior to and 24 hr after the first (BT) and last (AT) exercise session, and at the same time points for C. E performed ten upper and lower body resistance exercises (3 sets, 8 rep/set, 80% 1-RM) 3 times per week for 12 weeks; while C attended education classes twice per week for 12 weeks. Serum was assayed for total cholesterol, triglycerides, LDL-C, HDL-C, HDL2-C, HDL3-C concentrations. A 2 x 2 x 2 (group x training period x time) MANOVA was to determine changes in lipid and lipoprotein variables. A 2 x 2 (group x time) repeated measures ANOVA was used to assess body composition. RESULTS: The MANOVA revealed no significant changes in serum lipids or lipoproteins following RE or RT. No changes in body composition were observed post-training (P \u3e 0.05). Variable Pre-BT 24 hr BT Pre-AT 24 hr AT TC (mg/dl) C E 189 ± 28 217 ± 55 205 ± 40 212 ± 49 201 ± 48 207 ± 105 206 ± 42 195 ± 106 Tg (mg/dl) C E 107 ± 42 114 ± 40 96 ± 49 103 ± 25 116 ± 49 129 ± 92 112 ± 45 102 ± 48 LDL-C (mg/dl) C E 112 ± 26 140 ± 51 129 ± 37 137 ± 41 118 ± 40 127 ± 89 124 ± 41 120 ± 88 HDL-C (mg/dl) C E 55 ± 16 55 ± 12 57 ± 14 55 ±16 60 ± 13 53 ± 15 60 ± 16 54 ± 17 HDL2-C (mg/dl) C E 36 ± 12 36 ± 10 35 ± 10 34 ± 13 35 ± 12 33 ± 14 33 ± 16 35 ± 13 HDL3-C (mg/dl) C E 19 ± 9 19 ± 5 21 ± 7 21 ± 6 25 ± 6 20 ± 5 26 ± 6 20 ± 7 CONCLUSION: These data suggest that a single RE session and a 12-week RT program have no effect on lipids and lipoproteins. Compared to the effects of aerobic training, resistance exercise related changes in body composition may be necessary to modify lipids and lipoproteins in obese postmenopausal women