Fat Disposal Research Articles

Nutritional Interventions with Bacillus coagulans Improved Glucose Metabolism and Hyperinsulinemia in Mice with Acute Intermittent Porphyria.

Acute intermittent porphyria (AIP) is a metabolic disorder caused by mutations in the porphobilinogen deaminase (PBGD) gene, encoding the third enzyme of the heme synthesis pathway. Although AIP is characterized by low clinical penetrance (~1% of PBGD mutation carriers), patients with clinically stable disease report chronic symptoms and frequently show insulin resistance. This study aimed to evaluate the beneficial impact of nutritional interventions on correct carbohydrate dysfunctions in a mouse model of AIP that reproduces insulin resistance and altered glucose metabolism. The addition of spores of Bacillus coagulans in drinking water for 12 weeks modified the gut microbiome composition in AIP mice, ameliorated glucose tolerance and hyperinsulinemia, and stimulated fat disposal in adipose tissue. Lipid breakdown may be mediated by muscles burning energy and heat dissipation by brown adipose tissue, resulting in a loss of fatty tissue and improved lean/fat tissue ratio. Probiotic supplementation also improved muscle glucose uptake, as measured using Positron Emission Tomography (PET) analysis. In conclusion, these data provide a proof of concept that probiotics, as a dietary intervention in AIP, induce relevant changes in intestinal bacteria composition and improve glucose uptake and muscular energy utilization. Probiotics may offer a safe, efficient, and cost-effective option to manage people with insulin resistance associated with AIP.

Molecular and histological traits of reduced lysosomal acid lipase activity in the fatty liver

Recent studies demonstrated reduced blood lysosomal acid lipase (LAL) activity in patients with nonalcoholic fatty liver disease (NAFLD). We aimed to verify hepatic LAL protein content and activity in in vitro and in vivo models of fat overload and in NAFLD patients. LAL protein content and activity were firstly evaluated in Huh7 cells exposed to high-glucose/high-lipid (HGHL) medium and in the liver of C57BL/6 mice fed with high-fat diet (HFD) for 4 and 8 months. LAL protein was also evaluated by immunohistochemistry in liver biopsies from 87 NAFLD patients and 10 controls, and correlated with hepatic histology. Huh7 cells treated with HGHL medium showed a significant reduction of LAL activity, which was consistent with reduced LAL protein levels by western blotting using an antibody towards the N-term of the enzyme. Conversely, antibodies towards the C-term of the enzyme evidenced LAL accumulation, suggesting a post-translational modification that masks the LAL N-term epitope and affects enzymatic activity. Indeed, we found a high rate of ubiquitination and extra-lysosomal localization of LAL protein in cells treated with HGHL medium. Consistent with these findings, inhibition of proteasome triggered dysfunctional LAL accumulation and affected LAL activity. Accumulation of ubiquitinated/dysfunctional LAL was also found in the liver of HFD fed mice. In NAFLD patients, hepatic levels of non-ubiquitinated/functional LAL were lower than in controls and inversely correlated with disease activity and some of the hallmarks of reduced LAL. Fat overload leads to LAL ubiquitination and impairs its function, possibly reducing hepatic fat disposal and promoting NAFLD activity.

An overview of deregulated lipid metabolism in nonalcoholic fatty liver disease with special focus on lysosomal acid lipase.

Obesity and type 2 diabetes are frequently complicated by excess fat accumulation in the liver, which is known as nonalcoholic fatty liver disease (NAFLD). In this context, liver steatosis develops as a result of the deregulation of pathways controlling de novo lipogenesis and fat catabolism. Recent evidences suggest the clinical relevance of a reduction in the activity of lysosomal acid lipase (LAL), which is a key enzyme for intracellular fat disposal, in patients with NAFLD. In this review, we provided a comprehensive overview of the critical steps in hepatic fat metabolism and alterations in these pathways in NAFLD, with a special focus on lipophagy and LAL activity. During NAFLD, hepatic fat metabolism is impaired at several levels, which is significantly contributed to by impaired lipophagy, in which reduced LAL activity may play an important role. For further research and intervention in NAFLD, targeting LAL activity may provide interesting perspectives.

Geographies of fat waste. Or, how kitchen fats make citizens

While waste marks the beginning of relocation, re-materialization, and resourcing processes, it is also a set of connections, producing specific figurations of citizenship that follow from, as they inform, waste management strategies. This article regards household practices to do with the disposal of used fats as a site where citizenship forms. The authors see the figure of ‘good citizen’ appear along the trajectory of kitchen fats. They contrast this figure with the ‘re-user,’ who acts by a different set of rules, so as to explore logics and normativities embedded in the mundane processes of discarding fats. Fat waste not only turns out to be different things for different stakeholders; it is in different fat disposal practices that different (kinds of) stakeholders emerge. As the authors situate citizenship in mundane practices, kitchen fats suggest the situational, material-relational character of waste and waste-eliminating schemes – and of citizenship itself.

Recent advances in biomarkers for noninvasive diagnosis of nonalcoholic steatohepatitis: the role of lipid analysis/ profiling

Abnormalities of lipid metabolism may be involved in hepatic steatosis, which is a prerequisite for development of nonalcoholic steatohepatitis. In fact, most of the published literature has focused on triglyceride accumulation as the key defect in nonalcoholic fatty liver disease (NAFLD). Fat accumulation in the liver may be due to the excessive uptake of free fatty acids, increased liver lipogenesis, the impairment of fat disposal (as there is decreased β- and ω-oxidation of free fatty acids), and the decreased secretion of VLDL. The composition of lipids that accumulate in the livers of subjects with NAFLD are not well characterized, however, a number of recent studies have investigated the lipid profile in the livers and plasma of patients with nonalcoholic steatohepatitis. Several findings suggest that the altered lipid profiles may be important in the pathogenesis of NAFLD, whereas others emphasize that lipid alterations are an adaptive response to protect the liver against lipotoxicity. Interesting...

Fat, oil and grease - Sewer contamination prevention strategies and double-dosage concept for fat traps and pressure mains

Disposal of fat, oil and grease (FOG) in sewer systems cause blockages, fatal errors of pumping stations, increased maintenance, odours, hydrogen sulphide (H2S) emissions and corrosion. Hence, solutions to prevent FOG disposals are desirable. Challenges are prevention of FOG contamination of sewer systems and removal of FOG disposals. A survey and lab as well as full scale tests were performed. In the first place fat traps and grease inceptors should be installed to prevent FOG contamination what is documented as being very effective. A case study shows that the operation of fat traps may indeed produce further problems, especially H2S emissions, what demands an additional treatment. Removal of FOG disposals can be handled by applying enzymes to the affected sewer network. It was found that enzymes are preferable towards surfactants to remove FOG disposals. It appears to be a solution to have one dosing site that is equipped with separately controlled dosing pumps for conditioners for H2S removal as well as FOG removal.

Myostatin as a Potential Therapeutic Target for Obesity and Insulin Resistance

Considering that skeletal muscle is a major tissue responsible for whole body glucose and fat disposal, it has long been speculated that increasing muscle mass would be a potential therapeutic strategy to prevent obesity and fat-induced insulin resistance. Myostatin (growth differentiation factor 8, GDF8) is a transforming growth factor β (TGFβ) family member, and is known to act as a negative regulator of skeletal muscle differentiation and growth. Like other TGFβ members, dimeric myostatin mediates Sma/Mothers against decapentaplegic homolog (SMAD) signal transduction through its specific cell membrane receptors with serine/threonine kinase activity. Myostatin null (Mstn -/- ) mice exhibit a doubling of muscle mass due to muscle hypertrophy and hyperplasia, and are protected against fat-induced obesity and insulin resistance. Other genetic and pharmacologic approaches to inhibit myostatin activity also demonstrate an increase in muscle mass and a prevention of obesity and insulin resistance. This review will focus on the effects of myostatin inhibition on obesity and fat-induced insulin resistance, and will discuss the potential underlying mechanisms.

Meal Fatty Acid Uptake in Visceral Fat in Women

Differential meal fat uptake into adipose tissue depots may be a determinant of body fat distribution. We used the meal fat tracer/adipose tissue biopsy approach to compare the effects of meal fat content on the fat uptake into visceral and upper and lower body subcutaneous fat depots in 21 premenopausal women. [(3)H]triolein was used to trace the fate of fatty acids from a normal-fat or high-fat meal. The proportion of dietary fat uptake into the three depots did not differ between meals; visceral fat accounted for only approximately 5% of meal fat disposal irrespective of visceral fat mass. For the women consuming the normal-fat meal, the uptake of meal fatty acid into femoral fat (milligrams meal fat per gram lipid) increased as a function of leg fat mass (r = 0.68, P < 0.05), which we interpret as increased efficiency of uptake. The opposite pattern was seen in omental fat with the normal-fat meal and in all depots after the high-fat meal. For both meals, approximately 40% of meal fat was oxidized ((3)H(2)O production) after 24 h. We conclude that greater thigh adipose tissue in women is associated with greater efficiency of meal fat storage under conditions of energy balance, whereas the opposite is seen with visceral fat. These findings imply that different mechanisms may regulate fatty acid uptake in different depots, which may in turn impact on body fat distribution.

Insulin sensitivity is not related to regional fat gain in lean men and women

An upper body (UB) fat distribution is correlated with insulin resistance (IR). It is not known whether IR is caused by an UB fat distribution or if IR predisposes to UB fat gain. We recruited 25 lean volunteers to gain ~2 kg of body fat over ~8 weeks. We hypothesized that IR individuals would gain more UB fat than insulin sensitive individuals. At baseline, insulin sensitivity was assessed by 24-hour insulin AUC over a meal controlled inpatient stay. Meal fat disposal was measured by the meal fat tracer/fat biopsy approach. Participants were grouped into tertiles based on their AUC insulin: least insulin sensitive tertile 1 (T1) = 37,449±2600; middle tertile 2 (T2) = 22,11±3002; most insulin sensitive tertile 3 (T3)= 13,233±2452 uU/ml/24h (mean±sem). At baseline, volunteers in the different tertiles had significantly different % body fat (T1=29±2%, T2=22±2%, and T3=18±2%; P<0.005). The T1 had more upper body subcutaneous (UBSQ) fat at baseline (8.3±0.5 kg) than the T3 (6.1±0.5 kg; P<0.05). Visceral and lower body subcutaneous (LBSQ) fat at baseline did not differ significantly between tertiles. Baseline meal fat storage in LBSQ fat was greater in T1 than T3 (20.9±3.4% vs. 9.0±1.9%, P < 0.05). Changes in regional fat gain as a percentage of total fat gain was not different by tertiles (53.3±2.7%, 8.3±2.0%, and 37.8±1.8%, for UBSQ, visceral, and LBSQ). Baseline insulin sensitivity was not predictive of the proportion of fat gain in the visceral or UBSQ regions. This argues against the hypothesis that insulin resistance results in UB fat gain. The alternative explanation is that those who gain UB fat eventually develop IR. T3 stored the least meal fat in the LBSQ region, suggesting that regional fat depots have differing responses to the prevailing insulinemia, perhaps through regulation of LPL activity.

Role of inflammation in nonalcoholic steatohepatitis

Products of hepatic macrophages and lymphocytes are acknowledged regulators of liver injury and repair. Recent studies have identified inflammatory modulators from sources within and outside the liver that are critical to the pathogenesis and progression of chronic liver diseases, including nonalcoholic fatty liver disease. This review will focus on these developments to clarify how inflammatory mediators from adipose tissue and the liver interact to mediate the pathogenesis of nonalcoholic fatty liver disease. Hepatic steatosis and steatohepatitis are extremely prevalent in obese individuals with the metabolic syndrome. The metabolic syndrome results from abnormal production of various adipose-derived and liver-derived factors that modulate energy substrate flux to coordinate tissue anabolism and catabolism. Individuals with the metabolic syndrome produce a relative excess of proinflammatory factors. Some factors inhibit hepatic fat disposal and promote lipid accumulation within hepatocytes. The latter induces sustained hepatic generation of proinflammatory cytokines, particularly when the hepatic innate immune system becomes Th-1 polarized. Although chronic inflammation induces production of various profibrogenic factors, progression to latter stages of nonalcoholic fatty liver disease is relatively unusual in individuals with the metabolic syndrome. This may reflect requirements for additional factors that become abundant only in individuals who have additional defects in hepatic innate immunity. Obesity and the metabolic syndrome represent chronic inflammatory states and are associated with nonalcoholic fatty liver disease. Liver injury that ensues is dictated by metabolic and immunomodulatory factors that are produced by adipose tissue and within the liver.

Severely dysregulated disposal of postprandial triacylglycerols exacerbates hypertriacylglycerolemia in HIV lipodystrophy syndrome2–3

The pathogenesis of hypertriacylglycerolemia, a characteristic feature of HIV lipodystrophy syndrome (HLS), is incompletely understood. One mechanism is accelerated lipolysis in the fasted state, but the severity of the hypertriacylglycerolemia suggests that additional underlying abnormalities may exist in the disposal of dietary fat. Our objective was to investigate abnormalities in dietary fat disposal in the pathogenesis of hypertriacylglycerolemia in HLS. We studied 6 nondiabetic men with HLS and 6 men without HIV matched for age and body mass index as control subjects for 8 h after consumption of an isocaloric meal containing 2 g labeled [(13)C(3)]tripalmitin. Chylomicron-triacylglycerol disposal was estimated from labeled [(13)C(1)]palmitate in the plasma chylomicron fraction, and [(13)C(1)]palmitate oxidation was estimated from the (13)CO(2) enrichment in the breath and CO(2) production, over 8 h after the meal. HLS patients had significantly elevated concentrations of fasting plasma triacylglycerols in both chylomicron (x + SE: 100.3 +/- 49.5 compared with 29.2 +/- 2.2 mg/dL; P < 0.01) and VLDL (82.4 +/- 39.0 compared with 10.8 +/- 2.8 mg/dL; P < 0.01) fractions. Chylomicron-triacylglycerol-derived [(13)C(1)]palmitate disposal was markedly lower in the HLS patients (3.09 +/- 0.41 compared with 6.42 +/- 0.18 mmol [(13)C(1)]palmitate/8 h; P < 0.001) in the 8-h postmeal period. Further, HLS patients had lowered storage of chylomicron-triacylglycerols (0.74 +/- 0.38 compared with 5.05 +/- 0.16 mmol; P < 0.0001) and elevated plasma [(13)C(1)]palmitate concentrations (2.01 +/- 0.27 compared with 1.18 +/- 0.16 mmol; P < 0.05) 8 h after the meal. Patients with HLS have key defects that markedly impair postprandial disposal and storage of chylomicron-triacylglycerols. These defects contribute significantly to hypertriacylglycerolemia in HLS.