scholarly journals Single-cell chromatin accessibility and lipid profiling reveals SCD1-dependent metabolic shift in adipocytes induced by bariatric surgery

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261783
Author(s):  
Blaine Harlan ◽  
Hui Gyu Park ◽  
Roman Spektor ◽  
Bethany Cummings ◽  
J. Thomas Brenna ◽  
...  

Obesity promotes type 2 diabetes and cardiometabolic pathologies. Vertical sleeve gastrectomy (VSG) is used to treat obesity resulting in long-term weight loss and health improvements that precede weight loss; however, the mechanisms underlying the immediate benefits remain incompletely understood. Because adipose plays a crucial role in energy homeostasis and utilization, we hypothesized that VSG exerts its influences, in part, by modulating adipose functional states. We applied single-cell ATAC sequencing and lipid profiling to inguinal and epididymal adipose depots from mice that received sham surgery or VSG. We observed depot-specific cellular composition and chromatin accessibility patterns that were altered by VSG. Specifically, accessibility at Scd1, a fatty acid desaturase, was substantially reduced after VSG in mature adipocytes of inguinal but not epididymal depots. This was accompanied by reduced accumulation of SCD1-produced unsaturated fatty acids. Given these findings and reports that reductions in Scd1 attenuate obesity and insulin resistance our results suggest VSG exerts its beneficial effects through an inguinal depot-specific reduction of SCD1 activity.

2021 ◽  
Author(s):  
Blaine Harlan ◽  
Hui Gyu Park ◽  
Roman Spektor ◽  
Bethany Cummings ◽  
J Thomas Brenna ◽  
...  

Obesity promotes type 2 diabetes and cardiometabolic pathologies. Vertical sleeve gastrectomy (VSG) is used to treat obesity resulting in long-term weight loss and health improvements that precede weight loss; however, the mechanisms underlying the immediate benefits remain incompletely understood. Because adipose plays a crucial role in energy homeostasis and utilization, we hypothesized that VSG exerts its influences, in part, by modulating adipose functional states. We applied single-cell ATAC sequencing and lipid profiling to inguinal and epididymal adipose depots from mice that received sham surgery or VSG. We observed depot-specific cellular composition and chromatin accessibility patterns that were altered by VSG. Specifically, accessibility at Scd1, a fatty acid desaturase, was substantially reduced after VSG in mature adipocytes of inguinal but not epididymal depots. This was accompanied by reduced accumulation of SCD1-produced unsaturated fatty acids. Given these findings and reports that reductions in Scd1 attenuate obesity and insulin resistance and that unsaturated fatty acids stimulate glucose uptake, storage, and oxidation, our results suggest VSG exerts its beneficial effects through modifications of fatty acid profiles mediated by Scd1.


Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 286
Author(s):  
Nicola Marrano ◽  
Giuseppina Biondi ◽  
Anna Borrelli ◽  
Angelo Cignarelli ◽  
Sebastio Perrini ◽  
...  

Incretins are gut hormones that potentiate glucose-stimulated insulin secretion (GSIS) after meals. Glucagon-like peptide-1 (GLP-1) is the most investigated incretin hormone, synthesized mainly by L cells in the lower gut tract. GLP-1 promotes β-cell function and survival and exerts beneficial effects in different organs and tissues. Irisin, a myokine released in response to a high-fat diet and exercise, enhances GSIS. Similar to GLP-1, irisin augments insulin biosynthesis and promotes accrual of β-cell functional mass. In addition, irisin and GLP-1 share comparable pleiotropic effects and activate similar intracellular pathways. The insulinotropic and extra-pancreatic effects of GLP-1 are reduced in type 2 diabetes (T2D) patients but preserved at pharmacological doses. GLP-1 receptor agonists (GLP-1RAs) are therefore among the most widely used antidiabetes drugs, also considered for their cardiovascular benefits and ability to promote weight loss. Irisin levels are lower in T2D patients, and in diabetic and/or obese animal models irisin administration improves glycemic control and promotes weight loss. Interestingly, recent evidence suggests that both GLP-1 and irisin are also synthesized within the pancreatic islets, in α- and β-cells, respectively. This review aims to describe the similarities between GLP-1 and irisin and to propose a new potential axis–involving the gut, muscle, and endocrine pancreas that controls energy homeostasis.


Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1844-P
Author(s):  
AHMAD AL-MRABEH ◽  
SVIATLANA V. ZHYZHNEUSKAYA ◽  
ALISON C. BARNES ◽  
KIEREN G. HOLLINGSWORTH ◽  
NAVEED SATTAR ◽  
...  
Keyword(s):  

Diabetes ◽  
2021 ◽  
Vol 70 (Supplement 1) ◽  
pp. 564-P
Author(s):  
DANIEL COX ◽  
MATTHEW A. MONCRIEF ◽  
ANTHONY L. MCCALL

2015 ◽  
Vol 03 (01) ◽  
pp. 061-063
Author(s):  
Sandra Scrivens

AbstractWith global obesity affecting 475 million people worldwide, the continued popularity of celebrity or fad diets is not surprising. Evidence for their sustainability and long-term positive benefits on weight loss and cardiometabolic risk is, however, limited. Modest weight loss of 5-10% in overweight or obesity is associated with improvements in blood lipids, glycemia, and insulin resistance. As overweight and obesity are the main risk factors for Type 2 diabetes (T2DM), medical nutrition therapy based on a balanced, reduced total energy diet, tailored to the individual, is recommended by the American Diabetes Association, Diabetes UK and transcultural diabetes-specific nutrition algrorithm (tDNA) guidelines.


2020 ◽  
Vol 79 (4) ◽  
pp. 498-513 ◽  
Author(s):  
Chaitong Churuangsuk ◽  
Michael E. J. Lean ◽  
Emilie Combet

Low-carbohydrate diets (LCD) have been promoted for weight control and type 2 diabetes (T2D) management, based on an emerging body of evidence, including meta-analyses with an indication of publication bias. Proposed definitions vary between 50 and 130 g/d, or <10 and <40 % of energy from carbohydrate, with no consensus on LCD compositional criteria. LCD are usually followed with limited consideration for other macronutrients in the overall diet composition, introducing variance in the constituent foods and in metabolic responses. For weight management, extensive evidence supports LCD as a valid weight loss treatment, up to 1–2 years. Solely lowering carbohydrate intake does not, in the medium/long term, reduce HbA1c for T2D prevention or treatment, as many mechanisms interplay. Under controlled feeding conditions, LCD are not physiologically or clinically superior to diets with higher carbohydrates for weight-loss, fat loss, energy expenditure or glycaemic outcomes; indeed, all metabolic improvements require weight loss. Long-term evidence also links the LCD pattern to increased CVD risks and mortality. LCD can lead to micronutrient deficiencies and increased LDL-cholesterol, depending on food selection to replace carbohydrates. Evidence is limited but promising regarding food choices/sources to replace high-carbohydrate foods that may alleviate the negative effects of LCD, demanding further insight into the dietary practice of medium to long term LCD followers. Long-term, high-quality studies of LCD with different food sources (animal and/or plant origins) are needed, aiming for clinical endpoints (T2D incidence and remission, cardiovascular events, mortality). Ensuring micronutrient adequacy by food selection or supplementation should be considered for people who wish to pursue long-term LCD.


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