Insulin-stimulated lipogenesis gets an epigenetic makeover

Manuel, Clarence R.; Haeusler, Rebecca A.

doi:10.1172/jci137050

Cited by 8 publications

(5 citation statements)

References 11 publications

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“…It is due to autosomal-recessive portions of protein and fat to ease its future-use in patients with heart, renal and liver diseases without muscle wasting [10], and 2) 12-hour meals-separation to surpass the 8-hours 50% liver-ability of glycogenolysis and hence shift to muscle glycogenolysis and subcutaneous lipolysis using their lactate, pyruvate, glycerol, and amino acids [11]. On the other hand, our exercise technique consisted of; 1) acceptable protocol of 45 minutes thrice-weekly active walk rather than rigid daily practice to ease compliance and avoid injuries, 2) active straight walking without knee twisting to avoid its common injury in obese patients, 3) active abdominal movement and belly-fat squeezing to ease central obesity, and 4) after-burn (avoiding food for 1 hour after exercise) to assist in further breakdown of muscle fats by avoiding food-induced insulin lipogenesis [12]. Such calculated calory-loss of 350 -400/session is an acceptable muscle training to catabolize more fats and proteins [13].…”

Section: Discussionmentioning

confidence: 99%

The Beneficial Effect of 12-Hour Fasting, 45 Minutes Exercise Thrice Weekly and Their Combination on Weight Loss, Anthropometric Measures and Metabolic Syndrome

El-Reshaid¹,

Al-Bader²,

Ghanem³

2023

FNS

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Background: Obesity is the leading preventable cause of death worldwide. It is associated with significant increases in morbidity and mortality. Few studies have addressed, prospectively, the impact of life-style modification in weight-reduction in 1) morbidly obese patients with BMI > 35 kg/m 2 and 2) on its associated co-morbid risk factors for metabolic syndrome viz. high blood pressure, diabetes, hyperlipidemia and steatohepatitis as well as psychiatric disorders. Patients and Methods: We prospectively evaluated the role of 1) two meals daily with in between 12-hour fasting, 2) thrice weekly 45-minute active-walk, and 3) their combination, in management of ambulant obese patients, at BMI of 35 to 39.9 kg/m 2 who had such multiple acquired metabolic disorders. The study was conducted over 3 years with 45 patients in 3 matched groups with regards to gender, age, BMI, waist circumference, lipid profile (LDL and TG), fibroscan steatosis grade, psychiatric assessment, antidiabetic drugs and antihypertensive ones. Results: At 6 and 12 months, the 3 regimens were well tolerated and were effective in weight loss, improvement in anthropometric measures and management of metabolic syndrome yet the combined one was significantly better in all endpoints. Conclusion: Our protocols of exercise and dieting were effective measures in managing obesity and its associated co-morbidities and their combination is synergetic.

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Section: Discussionmentioning

confidence: 99%

The Beneficial Effect of 12-Hour Fasting, 45 Minutes Exercise Thrice Weekly and Their Combination on Weight Loss, Anthropometric Measures and Metabolic Syndrome

El-Reshaid¹,

Al-Bader²,

Ghanem³

2023

FNS

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“…Hence, identification of mechanisms underlying these processes is potentially conducive to the development of target approaches. It has been addressed in the last decade that histone demethylases are crucial regulators of hepatic lipogenesis as well as lipid influx and metabolism (Manuel and Haeusler 2020 ; Nagaoka et al 2015 ). In this study, we identified that ISL1 had interacted with H3K27me3 demethylase KDM6B to promote the expression of SNAI1, by which lipogenesis and steatosis were attenuated while lipolysis was promoted in the mice models of NAFLD (Fig.…”

Section: Discussionmentioning

confidence: 99%

Synergistic effects of ISL1 and KDM6B on non-alcoholic fatty liver disease through the regulation of SNAI1

Zhao

Pan

et al. 2022

Mol Med

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Background The increasing incidence of non-alcoholic fatty liver disease (NAFLD) has been reported worldwide, which urges understanding of its pathogenesis and development of more effective therapeutical methods for this chronic disease. In this study, we aimed to investigate the effects of a LIM homeodomain transcription factor, islet1 (ISL1) on NAFLD. Methods Male C57BL/6J mice were fed with a diet high in fat content to produce NAFLD models. These models were then treated with overexpressed ISL1 (oe-ISL1), oe-Lysine-specific demethylase 6B (KDM6B), oe-SNAI1, or short hairpin RNA against SNAI1. We assessed triglyceride and cholesterol contents in the plasma and liver tissues and determined the expressions of ISL1, KDM6B and SNAI1 in liver tissues. Moreover, the in vitro model of lipid accumulation was constructed using fatty acids to explore the in vitro effect of ISL1/KDM6B/SNAI1 in NAFLD. Results The results showed that the expressions of ISL1, KDM6B, and SNAI1 where decreased, but contents of triglyceride and cholesterol increased in mice exposed to high-fat diet. ISL1 inhibited lipogenesis and promoted lipolysis and exhibited a synergizing effect with KDM6B to upregulate the expression of SNAI1. Moreover, both KDM6B and SNAI1 could inhibit lipogenesis and induce lipolysis. Importantly, the therapeutic effects of ISL1 on in vitro model of lipid accumulations was also confirmed through the modulation of KDM6B and SNAI1. Conclusions Taken together, these findings highlighted that ISL1 effectively ameliorated NAFLD by inducing the expressions of KDM6B and SNAI1, which might be a promising drug for the treatment of NAFLD.

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“…Insulin signaling in the liver is known to induce hepatic de novo lipogenesis by activating transcription factors and enzymes involved in fatty acid biosynthesis [78,79]. Whether the liver changes that necessitated the termination of the IMAGINE program were adaptive changes to treatment with BIL or evidence of PEGylation-induced hepatotoxicity remains to be determined [38,41,80].…”

Section: The Imagine Trialsmentioning

confidence: 99%

Insulin Therapy for the Management of Diabetes Mellitus: A Narrative Review of Innovative Treatment Strategies

Nkonge,

Nkonge

2023

Diabetes Ther

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The discovery of insulin was presented to the international medical community on May 3, 1922. Since then, insulin has become one of the most effective pharmacological agents used to treat type 1 and type 2 diabetes mellitus. However, the initiation and intensification of insulin therapy is often delayed in people living with type 2 diabetes due to numerous challenges associated with daily subcutaneous administration. Reducing the frequency of injections, using insulin pens instead of syringes and vials, simplifying treatment regimens, or administering insulin through alternative routes may help improve adherence to and persistence with insulin therapy among people living with diabetes. As the world commemorates the centennial of the commercialization of insulin, the aims of this article are to provide an overview of insulin therapy and to summarize clinically significant findings from phase 3 clinical trials evaluating less frequent dosing of insulin and the non-injectable administration of insulin.

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Insulin-stimulated lipogenesis gets an epigenetic makeover

Cited by 8 publications

References 11 publications

The Beneficial Effect of 12-Hour Fasting, 45 Minutes Exercise Thrice Weekly and Their Combination on Weight Loss, Anthropometric Measures and Metabolic Syndrome

The Beneficial Effect of 12-Hour Fasting, 45 Minutes Exercise Thrice Weekly and Their Combination on Weight Loss, Anthropometric Measures and Metabolic Syndrome

Synergistic effects of ISL1 and KDM6B on non-alcoholic fatty liver disease through the regulation of SNAI1

Insulin Therapy for the Management of Diabetes Mellitus: A Narrative Review of Innovative Treatment Strategies

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