Liver-derived FGF21 is essential for full adaptation to ketogenic diet but does not regulate glucose homeostasis

Background: Obesity has become an increasingly worrisome reality. A very-low-calorie ketogenic diet (VLCKD) represents a promising option by which to achieve significant weight loss. This study sought to evaluate the effectiveness of VLCKD on metabolic parameters and hormonal profiles of obese male patients. Methods: We enrolled 40 overweight/obese men who consumed VLCKD for at least eight weeks. Body weight, waist circumference, fasting glucose, insulin, total cholesterol, high-density lipoprotein, triglycerides, creatinine, uric acid, aspartate aminotransferase, alanine aminotransferase, vitamin D, luteinizing hormone (LH), total testosterone (TT), and prostate-specific antigen (PSA) were calculated before and after VLCKD consumption. We additionally determined the homeostasis model assessment index and low-density lipoprotein (LDL) values. Results: After VLCKD (13.5 ± 0.83 weeks), the mean body weight loss was 21.05 ± 1.44 kg; the glucose homeostasis and lipid profile were improved significantly; serum vitamin D, LH, and TT levels were increased and the PSA levels were decreased significantly as compared with pretreatment values. These results are of interest since obesity can lead to hypogonadism and in turn, testosterone deficiency is associated with impaired glucose homeostasis, metabolic syndrome, and diabetes mellitus. Moreover, a close relationship between obesity, insulin resistance, and/or hyperinsulinemia and increased prostate volume has been reported, with a consequent greater risk of developing lower urinary tract symptoms. Conclusions: VLCKD is an effective tool against obesity and could be a noninvasive, rapid, and valid means to treat obese patients with metabolic hypogonadism and lower urinary tract symptoms.

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A very low carbohydrate ketogenic diet improves glucose tolerance in ob/ob mice independently of weight loss

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00357.2009 ◽

2009 ◽

Vol 297 (5) ◽

pp. E1197-E1204 ◽

Cited By ~ 88

Author(s):

Michael K. Badman ◽

Adam R. Kennedy ◽

Andrew C. Adams ◽

Pavlos Pissios ◽

Eleftheria Maratos-Flier

Keyword(s):

Gene Expression ◽

Weight Loss ◽

Ketogenic Diet ◽

Glucose Homeostasis ◽

Energy Homeostasis ◽

Caloric Intake ◽

Normal Weight ◽

Metabolic Effects ◽

Fibroblast Growth Factor 21 ◽

Low Carbohydrate

In mice of normal weight and with diet-induced obesity, a high-fat, low-carbohydrate ketogenic diet (KD) causes weight loss, reduced circulating glucose and lipids, and dramatic changes in hepatic gene expression. Many of the effects of KD are mediated by fibroblast growth factor 21 (FGF21). We tested the effects of KD feeding on ob/ ob mice to determine if metabolic effects would occur in obesity secondarily to leptin deficiency. We evaluated the effect of prolonged KD feeding on weight, energy homeostasis, circulating metabolites, glucose homeostasis, and gene expression. Subsequently, we evaluated the effects of leptin and fasting on FGF21 expression in ob/ ob mice. KD feeding of ob/ ob mice normalized fasting glycemia and substantially reduced insulin and lipid levels in the absence of weight loss. KD feeding was associated with significant increases in lipid oxidative genes and reduced expression of lipid synthetic genes, including stearoyl-coenzyme A desaturase 1, but no change in expression of inflammatory markers. In chow-fed ob/ ob mice, FGF21 mRNA was elevated 10-fold compared with wild-type animals, and no increase from this elevated baseline was seen with KD feeding. Administration of leptin to chow-fed ob/ ob mice led to a 24-fold induction of FGF21. Fasting also induced hepatic FGF21 in ob/ ob mice. Thus, KD feeding improved ob/ ob mouse glucose homeostasis without weight loss or altered caloric intake. These data demonstrate that manipulation of dietary macronutrient composition can lead to marked improvements in metabolic profile of leptin-deficient obese mice in the absence of weight loss.

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A ketogenic diet impairs energy and glucose homeostasis by the attenuation of hypothalamic leptin signaling and hepatic insulin signaling in a rat model of non-obese type 2 diabetes

Experimental Biology and Medicine ◽

10.1258/ebm.2010.010186 ◽

2011 ◽

Vol 236 (2) ◽

pp. 194-204 ◽

Cited By ~ 8

Author(s):

Sunmin Park ◽

Da Sol Kim ◽

Sunna Kang ◽

James W Daily

Keyword(s):

Type 2 Diabetes ◽

Ketogenic Diet ◽

Glucose Homeostasis ◽

Rat Model ◽

Insulin Signaling ◽

Leptin Signaling ◽

Hepatic Insulin Signaling

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Abstract #805711: Euglycemic Diabetic Ketoacidosis in a Patient with SGLT-2 Inhibitors Compounded by Ketogenic Diet

Endocrine Practice ◽

10.1016/s1530-891x(20)39640-3 ◽

2020 ◽

Vol 26 ◽

pp. 120

Author(s):

Sudha Nandala

Keyword(s):

Diabetic Ketoacidosis ◽

Ketogenic Diet ◽

Euglycemic Diabetic Ketoacidosis

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Supplementation with beta-hydroxy-beta-methylbutyrate impacts glucose homeostasis and increases liver size in trained mice

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000445 ◽

2020 ◽

Vol 90 (1-2) ◽

pp. 113-123

Author(s):

Ines Schadock ◽

Barbara G. Freitas ◽

Irae L. Moreira ◽

Joao A. Rincon ◽

Marcio Nunes Correa ◽

...

Keyword(s):

Strength Training ◽

Muscle Mass ◽

Glucose Homeostasis ◽

Fasting Blood Glucose ◽

Hepatic Metabolism ◽

Mass Gain ◽

Trained Group ◽

Tissue Mass ◽

Liver Size ◽

Intensive Training

Abstract. β-hydroxy-β-methyl butyrate (HMB) is a bioactive metabolite derived from the amino acid leucine, usually applied for muscle mass increase during physical training, as well as for muscle mass maintenance in debilitating chronic diseases. The hypothesis of the present study is that HMB is a safe supplement for muscle mass gain by strength training. Based on this, the objective was to measure changes in body composition, glucose homeostasis and hepatic metabolism of HMB supplemented mice during strength training. Two of four groups of male mice (n = 6/group) underwent an 8-week training period session (climbing stairs) with or without HMB supplementation (190 mg/kgBW per day). We observed lower body mass gain (4.9 ± 0.43% versus 1.2 ± 0.43, p < 0.001) and increased liver mass (40.9 ± 0.9 mg/gBW versus 44.8 ± 1.3, p < 0.001) in the supplemented trained group compared with the non-supplemented groups. The supplemented trained group had an increase in relative adipose tissue mass (12.4 ± 0.63 mg/gBW versus 16.1 ± 0.88, P < 0.01) compared to the non-supplemented untrained group, and an increase in fasting blood glucose (111 ± 4.58 mg/dL versus 122 ± 3.70, P < 0.05) and insulin resistance (3.79 ± 0.19 % glucose decay/min versus 2.45 ± 0.28, P < 0.05) comparing with non-supplemented trained group. Adaptive heart hypertrophy was observed only in the non-supplemented trained group (4.82 ± 0.05 mg/gBW versus 5.12 ± 0.13, P < 0.05). There was a higher hepatic insulin-like growth factor-1 expression (P = 0.002) in supplemented untrained comparing with non-supplemented untrained group. Gene expression of gluconeogenesis regulatory factors was increased by training and reduced by HMB supplementation. These results confirm that HMB supplementation associated with intensive training protocol drives changes in glucose homeostasis and liver metabolism in mice.

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