Ectopic fat deposition in populations of black African ancestry: A systematic review and meta-analysis

Aims In populations of black African ancestry (BA), a paradox exists whereby lower visceral adipose tissue is found despite their high risk for type 2 diabetes (T2D). This systematic review investigates ethnic differences in other ectopic fat depots (intrahepatic lipid: IHL; intramyocellular lipid: IMCL and intrapancreatic lipid; IPL) to help contextualise their potential contribution to T2D risk. Methods A systematic literature search was performed in December 2020 to identify studies reporting at least one ectopic fat comparison between BA and one/more other ethnicity. For IHL, a meta-analysis was carried out with studies considered comparable based on the method of measurement. Results Twenty-eight studies were included (IHL: n = 20; IMCL: n = 8; IPL: n = 4). Meta-analysis of 11 studies investigating IHL revealed that it was lower in BA populations vs pooled ethnic comparators (MD −1.35%, 95% CI −1.55 to −1.16, I2 = 85%, P < 0.00001), white European ancestry (MD −0.94%, 95% CI −1.17 to -0.70, I2 = 79%, P < 0.00001), Hispanic ancestry (MD −2.06%, 95% CI −2.49 to −1.63, I2 = 81%, P < 0.00001) and South Asian ancestry comparators (MD −1.92%, 95% CI −3.26 to −0.57, I2 = 78%, P = 0.005). However, heterogeneity was high in all analyses. Most studies found no significant differences in IMCL between BA and WE. Few studies investigated IPL, however, indicated that IPL is lower in BA compared to WE and HIS. Conclusion The discordance between ectopic fat and greater risk for T2D in BA populations raises questions around its contribution to T2D pathophysiology in BA.

Unsupervised Exercise Training Was Not Found to Improve the Metabolic Health or Phenotype over a 6-Month Dietary Intervention: A Randomised Controlled Trial with an Embedded Economic Analysis

Ectopic fat leads to metabolic health problems. This research aimed to assess the effectiveness of a hypocaloric diet intervention together with an unsupervised exercise training program in comparison with a hypocaloric diet alone to reduce ectopic fat deposition. Sixty-one premenopausal women with overweight or obesity participated in this controlled trial and were each randomised into either a usual care group (hypocaloric diet) or intervention group (hypocaloric diet + unsupervised exercise training). Ectopic fat deposition, metabolic parameters, incremental costs from a societal perspective and incremental quality-adjusted life years (QALYs) were assessed before, during and after the six-month intervention period. In the total sample, there was a significant decrease in visceral adipose tissue (VAT: −18.88 cm², 95% CI −11.82 to −25.95), subcutaneous abdominal adipose tissue (SAT: −46.74 cm², 95% CI −29.76 to −63.18), epicardial fat (ECF: −14.50 cm³, 95% CI −10.9 to −18.98) and intrahepatic lipid content (IHL: −3.53%, 95% CI −1.72 to −5.32). Consequently, an “adapted” economic analysis revealed a non-significant decrease in costs and an increase in QALYs after the intervention. No significant differences were found between groups. A multidisciplinary lifestyle approach seems successful in reducing ectopic fat deposition and improving the metabolic risk profile in women with overweight and obesity. The addition of unsupervised exercise training did not further improve the metabolic health or phenotype over the six months.

MAMs Protect Against Ectopic Fat Deposition and Lipid-Related Kidney Damage in DN Patients

Ectopic fat deposition (EFD) in the kidney plays a key role in the development of diabetic nephropathy (DN). Mitochondria-associated ER membranes (MAMs) are structures that connect to the endoplasmic reticulum (ER) and are involved in lipid metabolism. However, there are few studies on MAMs in the field of kidney disease, and the relationship between EFD and MAMs in DN is still unclear. In this study, increased EFD in the kidneys of DN patients was observed, and analysis showed that the degree of EFD was positively correlated with renal damage. Then, the MAMs were quantified by an in situ proximity ligation assay (PLA). The MAMs in the kidneys were found to gradually decrease through the different stages of DN, while the expression of ADRP (a marker of lipid droplets) and tubulointerstitial damage increased. Moreover, correlation analysis showed that the MAMs were negatively correlated with serum lipid levels, the EFD in the kidney and renal damage. Finally, we observed decreased expression of MAM-control proteins (DsbA-L, PACS-2, and MFN-2) in different stages of DN and they were associated with lipid deposition and renal damage. These data showed that the destruction of MAMs in DN might be the cause of EFD and interstitial damage in the kidney.

Mineralocorticoid receptors in the pathogenesis of insulin resistance and related disorders: From basic studies to clinical disease

Aldosterone is a steroid hormone that regulates blood pressure and cardiovascular function by acting on renal and vascular mineralocorticoid receptors (MRs) to promote sodium retention and modulate endothelial function. Indeed, MRs are expressed in endothelial cells, vascular smooth muscle cells, adipocytes, immune cells, skeletal muscle cells, and cardiomyocytes. Excessive aldosterone and associated MR activation impair insulin secretion, insulin metabolic signaling to promote development of diabetes and the related cardiometabolic syndrome. These adverse effects of aldosterone are mediated, in part, via increased inflammation, oxidative stress, dyslipidemia and ectopic fat deposition. Therefore, inhibition of MR activation may have a beneficial effect in prevention of impaired insulin metabolic signaling, type 2 diabetes and cardiometabolic disorders. This review highlights findings from the recent surge in research regarding MR related cardiometabolic disorders as well as our contemporary understanding of the detrimental effects of excess MR activation on insulin metabolic signaling.

Distinct Shades of Adipocytes Control the Metabolic Roles of Adipose Tissues: From Their Origins to Their Relevance for Medical Applications

Adipose tissue resides in specific depots scattered in peripheral or deeper locations all over the body and it enwraps most of the organs. This tissue is always in a dynamic evolution as it must adapt to the metabolic demand and constraints. It exhibits also endocrine functions important to regulate energy homeostasis. This complex organ is composed of depots able to produce opposite functions to monitor energy: the so called white adipose tissue acts to store energy as triglycerides preventing ectopic fat deposition while the brown adipose depots dissipate it. It is composed of many cell types. Different types of adipocytes constitute the mature cells specialized to store or burn energy. Immature adipose progenitors (AP) presenting stem cells properties contribute not only to the maintenance but also to the expansion of this tissue as observed in overweight or obese individuals. They display a high regeneration potential offering a great interest for cell therapy. In this review, we will depict the attributes of the distinct types of adipocytes and their contribution to the function and metabolic features of adipose tissue. We will examine the specific role and properties of distinct depots according to their location. We will consider their cellular heterogeneity to present an updated picture of this sophisticated tissue. We will also introduce new trends pointing out a rational targeting of adipose tissue for medical applications.

Duodenal-jejunal bypass improves nonalcoholic fatty liver disease independently of weight loss in rodents with diet-induced obesity

Our findings suggest that duodenal-jejunal bypass can reverse, independently of weight loss, ectopic fat deposition and insulin resistance, two features of nonalcoholic fatty liver disease that share a mutual pathway, in which perilipin-2 seems to be the main player. Our study supports further investigation into the role of proximal small intestine exclusion in the pathophysiology of nonalcoholic fatty liver disease to uncover less invasive treatments that mimic the effects of metabolic surgery and aims to prevent and treat metabolic liver disease.