Dysregulation of hepatic metabolism with obesity: factors influencing glucose and lipid metabolism

NAGARAJAN, .; Cross, Eloise; Sanna, Fabio; Hodson, Leanne

doi:10.1017/s0029665121003761

Cited by 30 publications

(16 citation statements)

References 97 publications

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“…Indeed, patients with NAFLD have a higher contribution of DNL-derived palmitate to VLDL-TG compared to non-NAFLD patients [5]. However, evidence for DNL as causative for the pathological IHTG accumulation is sparse, and it is likely pathological IHTG accumulation results from the perturbation of multiple metabolic pathways [34]. For example, it is plausible that pathways achieve a plateau when DNL increases beyond the capacity of VLDL secretion, thus predisposing an individual to IHTG accumulation.…”

Section: Discussionmentioning

confidence: 99%

Nutritional regulation of hepatic de novo lipogenesis in humans

Cross

Dearlove

Hodson

2023

Current Opinion in Clinical Nutrition &Amp; Metabolic Care

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Purpose of reviewDe novo lipogenesis (DNL) is a metabolic process occurring mainly within the liver, in humans. Insulin is a primary signal for promoting DNL; thus, nutritional state is a key determinant for upregulation of the pathway. However, the effects of dietary macronutrient composition on hepatic DNL remain unclear. Nor is it clear if a nutrition-induced increase in DNL results in accumulation of intra-hepatic triglyceride (IHTG); a mechanism often proposed for pathological IHTG. Here, we review the latest evidence surrounding the nutritional regulation of hepatic DNL.Recent findingsThe role of carbohydrate intake on hepatic DNL regulation has been well studied, with only limited data on the effects of fats and proteins. Overall, increasing carbohydrate intake typically results in an upregulation of DNL, with fructose being more lipogenic than glucose. For fat, it appears that an increased intake of n-3 polyunsaturated fatty acids downregulates DNL, whilst, in contrast, an increased dietary protein intake may upregulate DNL.SummaryAlthough DNL is upregulated with high-carbohydrate or mixed-macronutrient meal consumption, the effects of fat and protein remain unclear. Additionally, the effects of different phenotypes (including sex, age, ethnicity, and menopause status) in combination with different diets (enriched in different macronutrients) on hepatic DNL requires elucidation.

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Section: Discussionmentioning

confidence: 99%

Nutritional regulation of hepatic de novo lipogenesis in humans

Cross

Dearlove

Hodson

2023

Current Opinion in Clinical Nutrition &Amp; Metabolic Care

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“…Obesity is closely related to increased oxidative stress, lipid disorders and chronic inflammatory response [ 6 , 7 , 8 ], and the liver, adipocytes, immune cells and other systems are involved in the development and progression of obesity [ 9 ]. Metabolic diseases are associated with lipid and energy metabolism of various tissues, and liver and adipose tissue have important roles in maintaining body energy homeostasis [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Microbe-Derived Antioxidants Alleviate Liver and Adipose Tissue Lipid Disorders and Metabolic Inflammation Induced by High Fat Diet in Mice

Gao

Luo

et al. 2023

IJMS

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Obesity induces lipodystrophy and metabolic inflammation. Microbe-derived antioxidants (MA) are novel small-molecule nutrients obtained from microbial fermentation, and have anti-oxidation, lipid-lowering and anti-inflammatory effects. Whether MA can regulate obesity-induced lipodystrophy and metabolic inflammation has not yet been investigated. The aim of this study was to investigate the effects of MA on oxidative stress, lipid disorders, and metabolic inflammation in liver and epididymal adipose tissues (EAT) of mice fed with a high-fat diet (HFD). Results showed that MA was able to reverse the HFD-induced increase in body weight, body fat rate and Lee’s index in mice; reduce the fat content in serum, liver and EAT; and regulate the INS, LEP and resistin adipokines as well as free fatty acids to their normal levels. MA also reduced de novo synthesis of fat in the liver and EAT and promoted gene expression for lipolysis, fatty acid transport and β-oxidation. MA decreased TNF-α and MCP1 content in serum, elevated SOD activity in liver and EAT, induced macrophage polarization toward the M2 type, inhibited the NLRP3 pathway, increased gene expression of the anti-inflammatory factors IL-4 and IL-13 and suppressed gene expression of the pro-inflammatory factors IL-6, TNF-α and MCP1, thereby attenuating oxidative stress and inflammation induced by HFD. In conclusion, MA can effectively reduce HFD-induced weight gain and alleviate obesity-induced oxidative stress, lipid disorders and metabolic inflammation in the liver and EAT, indicating that MA shows great promise as a functional food.

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“…However, there has been no consensus as to whether the underlying mechanisms of obesity are definite risk factors for kidney dysfunction. Obesity is usually accompanied by metabolic abnormalities, including elevated blood glucose [ 9 ], elevated blood pressure [ 10 ], and lipid disorders [ 11 ]. Most studies declare that the metabolic abnormalities induced by obesity played a key role in kidney dysfunction [ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Metabolically healthy obesity is associated with higher risk of both hyperfiltration and mildly reduced estimated glomerular filtration rate: the role of serum uric acid in a cross-sectional study

Zhang

Chen

et al. 2023

J Transl Med

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Background The impact of metabolically healthy obesity (MHO) on kidney dysfunction remains debatable. Moreover, few studies have focused on the early stages of kidney dysfunction indicated by hyperfiltration and mildly reduced eGFR. Thus, we aimed to investigate the association between the MHO and early kidney dysfunction, which is represented by hyperfiltration and mildly reduced estimated glomerular filtration rate (eGFR), and to further explore whether serum uric acid affects this association. Methods This cross-sectional study enrolled 1188 residents aged ≥ 40 years old from Yonghong Communities. Metabolically healthy phenotypes were categorized based on Adult Treatment Panel III criteria. Obesity was defined as body mass index (BMI) ≥ 25 kg/m2. Mildly reduced eGFR was defined as being in the range 60 < eGFR ≤ 90 ml/min/1.73m2. Hyperfiltration was defined as eGFR > 95th percentile after adjusting for sex, age, weight, and height. Results Overall, MHO accounted for 12.8% of total participants and 24.6% of obese participants. Compared to metabolically healthy non-obesity (MHNO), MHO was significantly associated with an increased risk of mildly reduced eGFR (odds ratio [OR] = 1.85, 95% confidence interval [CI] 1.13–3.01) and hyperfiltration (OR = 2.28, 95% CI 1.03–5.09). However, upon further adjusting for uric acid, the association between the MHO phenotype and mildly reduced eGFR was reduced to null. Compared with MHNO/non-hyperuricemia, MHO/non-hyperuricemia was associated with an increased risk of mildly reduced eGFR (OR = 2.04, 95% CI 1.17–3.58), whereas MHO/hyperuricemia was associated with an observably increased risk (OR = 3.07, 95% CI 1.34–7.01). Conclusions MHO was associated with an increased risk of early kidney dysfunction, and the serum uric acid partially mediated this association. Further prospective studies are warranted to clarify the causality.

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Dysregulation of hepatic metabolism with obesity: factors influencing glucose and lipid metabolism

Cited by 30 publications

References 97 publications

Nutritional regulation of hepatic de novo lipogenesis in humans

Nutritional regulation of hepatic de novo lipogenesis in humans

Microbe-Derived Antioxidants Alleviate Liver and Adipose Tissue Lipid Disorders and Metabolic Inflammation Induced by High Fat Diet in Mice

Metabolically healthy obesity is associated with higher risk of both hyperfiltration and mildly reduced estimated glomerular filtration rate: the role of serum uric acid in a cross-sectional study

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