Mechanisms Linking Metabolic-Associated Fatty Liver Disease (MAFLD) to Cardiovascular Disease

Nonalcoholic fatty liver disease (NAFLD), sarcopenia and sarcopenic obesity (SO) are highly prevalent conditions that may coexist, especially in the aging population, without any approved pharmacologic treatment for all of them. There are multiple pathophysiologic mechanisms suggested to explain an association between NAFLD and sarcopenia or SO, including alterations in the adipokines, cytokines, hepatokines and myokines, which may interplay with other factors, such as aging, diet and physical inactivity. In clinical terms, most observational studies support an association between NAFLD and sarcopenia or SO; importantly, there are few cohort studies indicating higher mortality in patients with NAFLD and sarcopenia. Their association also bears some treatment considerations: for example, pioglitazone or vitamin E, suggested as off label treatment for selected patients with nonalcoholic steatohepatitis, may be recommended in the coexistence of sarcopenia or SO, since limited evidence did not show adverse effects of them on sarcopenia and abdominal obesity. In this review, evidence linking sarcopenia and SO with NAFLD is summarized, with a special focus on clinical data. A synopsis of the major pathophysiological links between NAFLD and sarcopenia/SO is initially presented, followed by selected clinical studies and, finally, treatment considerations in patients with NAFLD and sarcopenia or SO are discussed. 

Sarcopenia, sarcopenic obesity and nonalcoholic fatty liver disease.

Plastic pollution in the world is widespread and growing. The environment is swamped with nanoplastics (<100 nm), and the health consequences of these less visible pollutants are unknown. Furthermore, there is evidence that microplastics can release nanoplastics by digestive disintegration, implying that macroplastic exposure can cause direct and indirect disease via nanoplastics. The existence and impact of nanoplastics in numerous tissues from invertebrates to larger vertebrates that consume significant amounts of plastics were investigated, and histopathological techniques were utilized to determine physiological reactions and inflammation from the plastics. Nanoplastics enters an organism through the respiratory and gastro-intestinal tract where they accumulate into the liver through blood circulation via absorption, or epidermal infiltration. It is stated that macroplastics can cause damage directly at the site of exposure, whereas nanoplastics can influence the liver, causing subsequent damage to other organs. Multi-organ dysfunction is brought on by liver changes, and nanoplastics can readily enter the gut-liver axis and disturb the gut microflora. By exploring the literature and summarizing the research that has been published to date, this review article reveals the deleterious effect and mechanisms of nanoplastics on the pathophysiological functions of the hepatic system.

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Nanoplastics Toxicity Specific to Liver in Inducing Metabolic Dysfunction—A Comprehensive Review

Nonalcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases in the world. The risk factor for NAFLD is often considered to be obesity, but it can also occur in people with lean type, which is defined as lean NAFLD. Lean NAFLD is commonly associated with sarcopenia, a progressive loss of muscle quantity and quality. The pathological features of lean NAFLD such as visceral obesity, insulin resistance, and metabolic inflammation are inducers of sarcopenia, whereas loss of muscle mass and function further exacerbates ectopic fat accumulation and lean NAFLD. Therefore, we discussed the association of sarcopenia and lean NAFLD, summarized the underlying pathological mechanisms, and proposed potential strategies to reduce the risks of lean NAFLD and sarcopenia in this review.

/pdf/lean-nonalcoholic-fatty-liver-disease-and-sarcopenia-255eo9hy.pdf

Lean nonalcoholic fatty liver disease and sarcopenia

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects more than 30% of the world’s adult population. While it is associated with obesity and metabolic syndrome, emerging evidence has shown that a substantial number of MASLD patients have a normal body mass index (“lean individuals with MASLD”). In this article, we provide an overview of the definition, epidemiology, pathogenesis, and clinical outcomes associated with lean individuals with MASLD and updates on current management.

What Is New in Metabolic Dysfunction-Associated Steatotic Liver Disease in Lean Individuals: From Bench to Bedside

Background Few studies have specifically observed the relationship of sarcopenia, visceral obesity, or their joint effects with lean NAFLD in patients with diabetes. We aimed to investigate the associations of lean NAFLD with sarcopenia, visceral obesity, and sarcopenic visceral obesity (SV) in Chinese patients with type 2 diabetes mellitus (T2DM). Methods Altogether, 1,112 T2DM patients with BMI <25 kg/m2 were enrolled, and 33.18% of them were diagnosed with lean NAFLD by abdominal ultrasonography. Body composition markers were measured by bioelectrical impedance (BIA). Skeletal muscle mass index (SMI) was calculated as appendicular skeletal muscle mass (ASM) divided by weight, and sarcopenia was defined as SMI < 1 standard deviation (SD) below the sex-specific average for a young reference population. Visceral obesity was defined as visceral fat area (VFA) ≥ 100 cm2. Participants were categorized into one of the four body composition groups: nonsarcopenia/nonvisceral obesity (NN), nonsarcopenia/visceral obesity (NV), sarcopenia/nonvisceral obesity (SN), and SV. Results Compared to those in the NN group, patients in the NV and SN groups had a higher risk of lean NAFLD after full adjustments (NV: OR = 1.74; 95% CI: 1.09, 2.78; SN: OR =2.07; 95% CI: 1.23, 3.46). Of note, patients in the SV group had the highest odds of lean NAFLD (OR = 3.29; 95% CI: 2.10, 5.17). There were no significant interaction effects between sarcopenia and metabolic risk factors on prevalent lean NAFLD. Conclusions The current study demonstrated that SV was more closely associated with higher prevalent lean NAFLD than sarcopenia or visceral obesity alone in Chinese patients with T2DM. Besides, the harmful effect of sarcopenia on lean NAFLD was not influenced by visceral obesity or other metabolic risk factors. We hypothesize that increasing skeletal muscle mass more than just reducing visceral fat might be more optimal for the prevention and management of lean NAFLD, which needs further investigation in future studies.

/pdf/the-association-of-sarcopenia-and-visceral-obesity-with-lean-1tjkvqmr.pdf

The Association of Sarcopenia and Visceral Obesity with Lean Nonalcoholic Fatty Liver Disease in Chinese Patients with Type 2 Diabetes Mellitus

Association of non-alcoholic fatty liver disease with total testosterone in non-overweight/obese men with type 2 diabetes mellitus

We aimed to investigate the association of fruit and vegetable consumption with nonalcoholic fatty liver disease (NAFLD) in Chinese patients with type 2 diabetes mellitus (T2DM). This cross-sectional study included 2667 Chinese patients with T2DM aged 18 to 76 years from March 2017 to October 2021. Dietary intake was assessed using a food frequency questionnaire, and prevalent NAFLD was diagnosed with abdominal ultrasonography. High fruit–vegetable consumption was determined using ≥500 g/day consumption of both fruit and vegetable, and both fruit and vegetable consumption were divided into three categories of <200 g/day (low), 200–400 g/day (median) and >400 g (high). The primary outcome measurement was multivariate-adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for the prevalence of NAFLD in relation to the highest fruit and (or) vegetable intake compared with the lowest. Secondary analyses were conducted to assess the effects of either fruit or vegetable intake on the fatty liver index (FLI) using multivariable linear regressions. There were 1694 men and 973 women in this study, and 1445 (54.06%) participants had prevalent NAFLD. Patients with high fruit–vegetable intake had a lower prevalence of NAFLD than those with low fruit–vegetable intake (52.04% vs. 56.48%), but this difference was not statistically significant (p = 0.065). Vegetable intake had a significantly inverse association with NAFLD (OR: 0.68, 95% CI: 0.52–0.90), but this association was not pronounced with fruit intake (OR: 1.23, 95% CI: 0.89–1.69) or fruit–vegetable intake (OR: 0.90, 95% CI: 0.73–1.10). Additional analyses showed that an increase in vegetable intake was linearly associated with a significant reduction in FLI (β: −1.028, 95% CI: −1.836, −0.219). In conclusion, higher vegetable consumption was associated with lower odds of NAFLD in Chinese patients with T2DM, which suggested that increased vegetable intake might protect patients with diabetes against NAFLD.

/pdf/inverse-association-of-fruit-and-vegetable-consumption-with-11bufz3h.pdf

Inverse Association of Fruit and Vegetable Consumption with Nonalcoholic Fatty Liver Disease in Chinese Patients with Type 2 Diabetes Mellitus

Introduction The aim of this study was to investigate the associations of neck circumference (NC) and neck-to-height (NHR) with diabetic kidney disease (DKD) in Chinese patients with type 2 diabetes mellitus (T2DM). Materials and methods A total of 2,615 patients with prevalent T2DM were enrolled. NHR was calculated through NC (cm) divided by height (cm), and prevalent DKD was defined as the urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g or the estimated glomerular filtration rate (eGFR) < 60 ml/min per 1.73 m2 in the absence of other primary kidney diseases. Results The levels of NC and NHR were higher in DKD patients compared with non-DKD patients (38.22 vs. 37.71, P = 0.003; 0.232 vs. 0.227, P < 0.001, respectively). After full adjustments, individuals at the highest tertile of NHR had higher odds of DKD than those at the lowest tertile (multivariate-adjusted OR = 1.63, 95% CI: 1.22, 2.18), but this association was not pronounced with NC (multivariate-adjusted OR = 1.24, 95% CI: 0.87, 1.76). Individuals at the highest tertile of NHR had lower eGFR (β = -4.64, 95% CI: -6.55, -2.74) and higher UACR levels (β = 0.27, 95% CI: 0.10, 0.45) than those at the lowest tertile. The adverse association between NHR and prevalent DKD remained statistically significant among most of the subgroups analyzed and no interaction effects were observed. Conclusion The increase in NHR was adversely and independently associated with DKD in this Chinese T2DM population.

https://www.frontiersin.org/articles/10.3389/fendo.2022.1100354/pdf

Neck-to-height ratio is positively associated with diabetic kidney disease in Chinese patients with type 2 diabetes mellitus

Inverse association of healthy diet scores with non-alcoholic fatty liver disease among Chinese patients with type 2 diabetes mellitus.

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